bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein E Genotypes in Mexican Patients with Parkinson's Disease
Authors: Gallegos-Arreola M.P. , Figuera L.E. , Ortiz G.G. , Jiménez-Gil F.J. , Ramírez-Vega J. , Ruíz-Sandoval J.L. , Puebla-Pérez A.M. , Troyo-Sanroman R. , García-Ortiz J.E. , Sanchez-Corona J. , Zúñiga-González G.M.
Published: June 2013

Background: The association of the apolipoprotein (Apo E) -epsilon4 allele to neurodegenerative diseases such as Parkinson’s disease (PD) has been analyzed in several studies. This association has been identified by amyloid deposits and neurofibrillary tangles in the brains of patients with neurodegenerative diseases.

Method: In this study the possible relationship betweenApo Ealleles and PD patients was analyzed in 105 patients with PD and 107 healthy controls from a Mexican population.

Results: Allele analysis in PD vs. controls was: ε2in 6% and 2.3%, respectively; ε3in 73% and 88.3%; and ε4in 21% and 9.4%. The ε3allele showed a protective risk effect with an Odds ratio (OR) of 0.36 (95%CI 0.20-0.61) and p < 0.05; contrary results were observed for the ε4allele, which showed an increased risk for PD, with an OR of 2.57(95% CI 1.42-4.79) andp< 0.05. Upon multivariate analysis showed PD risk was evident in patients who were carriers of the genotype ε3/ε4; age group (fifty or more years) and had exposure to pesticides and solvents (p< 0.05).

Conclusions: The ε3/ε3; ε3/ε4genotypes of the Apo E, were positively associated with sporadic PD.
Clinical Implications of Adiponectin and Inflammatory Biomarkers in Type 2 Diabetes Mellitus
Authors: Swellam Menha , Sayed Mahmoud Magda , Abdel-Fatah Ali Adel
Published: June 2013

Objectives: To study the interrelationships of adiponectin, C-reactive protein (CRP) and fibrinogen with each other in T2DM patients with (T2DM-C) and without complications (T2DM-NC) among healthy individuals.

Design and methods: The study comprised of 120 T2DM-C, 59 T2DM-NC patients and 40 healthy volunteers. Biochemical markers were determined in the serum.

Results: Positivity rates of CRP and fibrinogen were significantly increased in T2DM-C as compared to T2DM-NC or controls, whereas adiponectin showed highest level in healthy individuals. Inflammatory biomarkers were inversely correlated with adiponectin (P< 0.01). Lipid profiles, kidney functions and BMI, showed positive significant correlation with CRP and fibrinogen but negative correlation with adiponectin. For better detection of T2DM, the combined sensitivity (98.9%) and specificity (92.5%) of fibrinogen and adiponectin was higher than the combined sensitivity and specificity of fibrinogen and CRP or adiponectin and CRP or than that of the biomarkers alone.

Conclusion: Elevated levels of CRP and fibrinogen and reduced level of adiponectin can be used for early diagnosis of T2DM and can predict diabetic complications.
Expression of Survivin and Cortactin in Colorectal Adenocarcinoma: Association with Clinicopathological Parameters
Authors: Lee Ying-Yu , Yu Cheng-Ping , Lin Chih-Kung , Nieh Shin , Hsu Kuo-Feng , Chiang Hung , Jin Jong-Shiaw
Published: June 2013

Objective: Survivin and cortactin are factors that promote tumor progression. We tested the hypothesis that survivin and cortactin expressions correlate with the clinico-pathological parameters of colorectal adenocarcinomas and survival time. Methods: Immunohistochemical analysis of survivin and cortactin were performed using tissue microarrays of 119 specimens from 18 well, 50 moderately, and 27 poorly differentiated colorectal adenocarcinomas and 24 colorectal adenomas with dysplasia. As control, 10 specimens of normal colorectal epithelia were included.

Results: The percentage of cells immunostained and the immunostaining scores for survivin and cortactin were all significantly higher in well-, moderately, and poorly differentiated colorectal adenocarcinomas than in normal colorectal epithelia. The survivin immunostaining score was significantly correlated with T, M, and AJCC/TNM stages (p `0.05). For cortactin, the score was significantly correlated with T and M stages (p ` 0.05). Higher survivin immunostaining score was associated with higher mortality.

Conclusions: Higher expression of survivin and cortactin correlates significantly with tumor stages and shorter survival time. Survivin and cortactin may be good biomarkers of aggressiveness of colorectal adenocarcinomas. Our findings require validation in independent cohorts and these data support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies.
DDAH2 mRNA Expression Is Inversely Associated with Some Cardiovascular Risk-Related Features in Healthy Young Adults
Authors: Puchau Blanca , Hermsdorff Helen Hermana M. , Zulet M. Ángeles , Martínez J. Alfredo
Published: June 2013

The purpose of this study was to evaluate whether the mRNA expression profiles of three genes (PRMT1, DDAH2 and NOS3) are related to ADMA metabolism and signalling, and the potential relationships with anthropometrical, biochemical, lifestyle and inflammatory indicators in healthy young adults. An emphasis on the putative effect of different mRNA expression on cardiovascular risk-related features was paid. Anthropometrical measurements as well as lifestyle features were analyzed in 120 healthy young adults. Fasting blood samples were collected for the measurement of glucose and lipid profiles as well as the concentrations of selected inflammatory markers. Profiles of mRNA expression were assessed for PRMT1, DDAH2 and NOS3 genes from peripheral blood mononuclear cells. Regarding inflammatory biomarkers, DDAH2 was inversely associated with IL-6 and TNF-α. Moreover, subjects in the highest quintile of DDAH2 mRNA expression showed a reduced risk to have higher values of waist circumference, and to be more prone to show higher values of HDL-c. Interestingly, DDAH2 gene expression seemed to be related with some anthropometrical, biochemical, lifestyle and inflammatory indicators linked to cardiovascular risk in apparently healthy young adults, emerging as a potential disease marker.
Progression Model Tissue Microarray (TMA) for the Study of Uterine Carcinomas
Authors: Arafa Mohammad , Boniver Jacques , Delvenne Philippe
Published: June 2013

Cervical and endometrial uterine carcinomas are heterogeneous groups of cancers, which are preceded by preneoplastic lesions. More accurate tools are needed to improve the diagnosis and to define markers which may be relevant for the diagnosis, prediction of disease progression and therapeutic response.

High throughput technologies for testing and validating molecular targets in cancer lesions and in their precursors are presently available. Among them, the tissue microarray (TMA) presents the advantage of a morphological control of the analyzed tissue fragment. In this article, we review the different aspects of the TMA technology with a special consideration to a uterine carcinogenesis model.
The Essential Role of DOCK8 in Humoral Immunity
Authors: Randall Katrina L. , Lambe Teresa , Goodnow Chris C. , Cornall Richard J.
Published: June 2013

The processes that normally generate and maintain adaptive immunity and immunological memory are poorly understood, and yet of fundamental importance when infectious diseases place such a major economic and social burden on the world's health and agriculture systems. Defects in these mechanisms also underlie the many forms of human primary immunodeficiency. Identifying these mechanisms in a systematic way is therefore important if we are to develop better strategies for treating and preventing infection, inherited disease, transplant rejection and autoimmunity. In this review we describe a genome-wide screen in mice for the genes important for generating these adaptive responses, and describe two independent DOCK8 mutant mice strains identified by this screen. DOCK 8 was found to play an essential role in humoral immune responses and to be important in the proper formation of the B cell immunological synapse.
Bladder Cancer Risk Associated with Genotypic Polymorphism of the Matrix Metalloproteinase-1 and 7 in North Indian Population
Authors: Srivastava Priyanka , Gangwar Ruchika , Kapoor Rakesh , Mittal Rama D.
Published: June 2013

Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk.

Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).MMP1-1607 2G/2G andMMP7-181 GG genotype were associated with increased risk of BC (p<0.001; OR, 3.04; 95% CI1.71–5.39 and p, 0.005; OR, 2.38; 95% CI1.30–4.34) respectively. Smokers in BC patients showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI1.40–7.31 and p, 0.009; OR, 2.85; 95% CI1.30–6.23 respectively). Haplotype analysis too revealed significant association with G/2G ofMMP1-519-1607 (p< 0.001; OR, 2.62; 95% CI1.68–4.09). The 2G allele carrier (1G/2G + 2G/2G) ofMMP1-1607 showed a protective effect and high recurrence free survival in Bacillus Calmette-Guerin (BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our datasuggested that MMP11607 2G and MMP7181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G+2G/2G) ofMMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure.
No Direct Association of Serotonin Transporter (STin2 VNTR) and Receptor (HT 102T>C) Gene Variants in Genetic Susceptibility to Migraine
Authors: Joshi Gunjan , Pradhan Sunil , Mittal Balraj
Published: June 2013

We aimed to find out if the serotonin receptor (HT102T>C) and serotonin transporter (STin 2) polymorphisms play any role in genetic susceptibility of migraine. For the study, 217 migraine patients and 217 healthy controls (HC) were recruited and genotyping was carried out using the Polymerase Chain Reaction and Restriction Fragment Length polymorphism (PCR-RFLP) method. All results were Bonferroni corrected. We could not find any significant differences in the genotype or allele frequencies in case of HT 102 T>C polymorphism between migraine patients and healthy controls (P value=0.224). No significant association was seen at allele and carrier levels. Sub-grouping the patients on the basis of gender or on basis of migraine type i.e. with or without aura also did not show any association. Similarly, no difference in genotype (P value=0.236), allele (P value=0.550) or carrier frequency (P value=0.771) in STin 2 VNTR polymorphism was observed between migraine patients. However, HT 102 TC genotype was observed to interact significantly with the STin 2.10/10 genotype in enhancing risk of migraine, both with and without aura. In conclusion, the HT102 T>C receptor and the STin 2 VNTR transporter polymorphisms, did not individually confer any significant risk of migraine or its clinical subtypes but the two polymorphisms appear to synergistically influence susceptibility to migraine. Serotonin transporter (STin2 VNTR) and receptor (HT 102T>C) polymorphisms; Migraine with aura (MA); Migraine without aura (MO); Genetic susceptibility
Association of Polymorphism in Cytochrome P450 2D6 and N-Acetyltransferase-2 with Parkinson’s Disease
Authors: Singh Madhu , Khanna Vinay K. , Shukla Rakesh , Parmar Devendra
Published: June 2013

The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2), that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency ofCYP2D6*2(1749G/C and 2938C/T),CYP2D6*4(1934G/A) andCYP2D6*10A(188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association ofCYP2D6*4(1934G/A) andCYP2D6*10A(188C/T) polymorphism with PD. Likewise, increased frequency ofNAT2*7polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95%CI: 0.56–54). No change was observed in the frequency ofNAT*5orNAT*6alleles in the cases. Further, cases carrying combination of heterozygous genotypes ofCYP2D6*4orCYP2D6*10A(188C > T) andNAT2*5were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD.
Potential Influence of Interleukin-1 Receptor Antagonist Gene Polymorphism on Knee Osteoarthritis Risk
Authors: Swellam Menha , Mahmoud Magda Sayed , Samy Nervana , Gamal Ali Ahmed
Published: June 2013

Objectives:Genes encoding for cytokines have been associated with susceptibility for joint osteoarthritis (OA) and interleukin (IL)-1 gene is supposed to be involved in the cartilage destruction process. In this regard, interleukin-1 receptor antagonist (IL-1RA) competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. We assessed the association of primary knee OA with IL-1RA region as a putative factor of susceptibility to knee OA in Egyptian patients.

Design and methods:Eighty patients with primary knee OA and 40 aged-matched healthy controls were included into the study. DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction (PCR) in both groups.

Results:An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was found in OA patients relative to controls (60.5% vs. 39.5%,P= 0.039, 85.4% vs. 14.6%,P= 0.002, respectively) however, only the carriage rate of IL-1RN*2 allele was found to be significant when OA patients were compared to the controls. Significant higher frequencies of IL-1RN*1/*2 and IL-1RN*2/*2 genotypes in OA patients were observed as compared with controls. Both visual analogue scale (VAS) and radiographic score revealed significant correlation with both the allelic frequency and the carriage rate of IL-1RN*2 allele. Moreover, absolute frequency of IL-1RN*1/*2 genotype OA patients revealed severe VAS and high radiographic score.

Conclusion:These results suggest that IL-1RN*2 allele represent a significant factor influencing the severity and course of knee OA; thereby supporting the potential role of IL-1 in the pathogenesis of this disease.
Diagnostic and Prognostic Utility of PD-1 In B Cell Lymphomas
Authors: Muenst S. , Hoeller S. , Willi N. , Dirnhofer S. , Tzankov A.
Published: June 2013

Aims: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas.

Methods: Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. Results: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells.

Conclusions: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.
Rapid Genotyping of the Human Renin (REN) Gene by the LightCycler® Instrument: Identification of Unexpected Nucleotide Substitutions within the Selected Hybridization Probe Area
Authors: Wee Line , Vefring Hege , Jonsson Grete , Jugessur Astanand , Lie Rolv Terje
Published: June 2013

Preeclampsia is a serious disorder affecting nearly 3% of all in the Western world. It is associated with hypertension and proteinuria, and several lines of evidence suggest that the renin-angiotensin system (RAS) may be involved in the development of hypertension at different stages of a preeclamptic pregnancy. In this study, we developed rapid genotyping assays on the LightCycler® instrument to allow the detection of genetic variants in the renin gene (REN) that may predispose to preeclampsia. The method is based on real-time PCR and allele-specific hybridization probes, followed by fluorescent melting curve analysis to expose a change in melting temperature (Tm). Ninety-two mother-father-child triads (n=276) from preeclamptic pregnancies were genotyped for three haplotype-tagging single nucleotide polymorphisms (htSNPs) inREN. All three htSNPs (rs5705, rs1464816 and rs3795575) were successfully genotyped. Furthermore, two unexpected nucleotide substitutions (rs11571084 and rs61757041) were identified within the selected hybridization probe area of rs1464816 and rs3795575 due to aberrant melting peaks. In conclusion, genotyping on the LightCycler® instrument proved to be rapid and highly reproducible. The ability to uncover additional nucleotide substitutions is particularly important in that it allows the identification of potentially etiological variants that might otherwise be overlooked by other genotyping methods.
Diagnostic and Prognostic Value of Circulating miR-221 for Extranodal Natural Killer/T-Cell Lymphoma
Authors: Guo Hong-Qiang , Huang Guo-Liang , Guo Cheng-Cheng , Pu Xing-Xiang , Lin Tong-Yu
Published: June 2013

Extra-nodal natural killer T-Cell (NK/T-cell) lymphoma is a progressive cancer with poor prognosis due to the lack of disease specific treatment. To develop specific therapeutic strategies, it is essential to identify tumor markers. Recent studies show that circulating microRNA (miRNA) may serve as diagnostic and/or prognostic markers for some diseases. To explore miRNAs as potential diagnostic and/or prognostic markers of NK/T-cell lymphoma, in our study, we compared circulating miR-221 levels in 79 patients and 37 normal subjects by real-time PCR amplification directly from plasma samples, and correlated patient's miR-221 levels with their clinic features and treatment outcomes. We observed a significant difference between the patient and control groups (p=0.038), and a correlation of plasma miR-221 level in patient with sex, as well as a reverse correlation with performance status and the overall survival after treatment. Univariate and multivariate analyses further revealed that plasma miR-221 level, age, B symptoms, LDH level and complete response after primary treatment all present prognostic values when judged by overall survival (OS). Together, our results show that it is feasible to perform direct amplification of plasma miRNAs without total RNA extraction, and plasma miR-221 may be a diagnostic and prognostic marker for NK/T-cell lymphoma.
Applicability of Antibody and mRNA Expression Microarrays for Identifying Diagnostic and Progression Markers of Early and Late Stage Colorectal Cancer
Authors: Spisák Sándor , Galamb Barnabás , Sipos Ferenc , Galamb Orsolya , Wichmann Barnabás , Solymosi Norbert , Nemes Balázs , Molnár Jeannette , Tulassay Zsolt , Molnár Béla
Published: June 2013

The exact molecular background and the connection between protein and mRNA expression in colorectal cancer (CRC) development and progression are not completely elucidated. Our purposes were the identification of protein markers of colorectal carcinogenesis and progression using protein arrays and validation on tissue microarrays. The connection between antibody and mRNA expression array results was also examined. Using cancerous and adjacent normal samples from 10 patients with early and 6 with advanced CRC, 67 differentially expressed genes were identified between normal and cancerous samples. A marker set containing 6 proteins (CCNA1, AR, TOP1, TGFB, HSP60, ERK1) was developed which could differentiate normal specimen, early and late stage CRC with high sensitivity and specificity. Dukes D stage samples were analyzed on HGU133plus2.0 microarrays. In these samples, mRNA and protein expression of 143 genes showed strong positive correlations (R2> 0.8), while a negative correlation (R2> 0.9) was found in case of 95 genes. Based on our results a correlation could be established between transcriptome and antibody array results, hence the former may be used as a high-capacity screening method before applying antibody arrays containing already planned targets. Antibody microarrays may have a fundamental importance in testing of marker combinations and future application in diagnostics of tumorous diseases.
A Polymorphism of the Corticotropin-Releasing Hormone Receptor 2 (CRHR2) and Preterm Birth
Authors: Schmid Maximilian , Grimm Christoph , Leipold Heinz , Knöfler Martin , Haslinger Peter , Egarter Christian
Published: June 2013

Our aim was to investigate whether a genetic variation in the corticotropin-releasing hormone receptor 2 gene might be associated with preterm birth. In this case-control study we evaluated the G/A polymorphism (rs2267717) in intron 2 of the corticotropin-releasing hormone receptor 2 gene in one hundred women with preterm birth and one hundred healthy women with at least one uncomplicated full term pregnancy and no history of preterm birth. No significant correlation was found between the presence of the investigated polymorphism and preterm birth (p= 0.9, odds ratio 0.9 [Confidence interval 0.5–1.7]). A dose dependent association of the investigated polymorphism, in women with preterm birth, with gestational age at delivery (p= 0.003) and birth weight was observed (p= 0.0001). However, no association between IUGR (n=10) with either one of the investigated genotypes (p= 0.3) was found. Stratified analysis within case group (i.e. PPROM vs. non-PPROM) revealed no significant difference in genotype distribution (p= 0.6). In conclusion, the investigated polymorphism does not increase the risk for preterm birth overall but might modulate the length of pregnancy in a dose dependent fashion in a series of Caucasian women.
Analysis of Polymorphisms in Genes (AGT,MTHFR,GPIIIa, andGSTP1) Associated with Hypertension, Thrombophilia and Oxidative Stress in Mestizo and Amerindian Populations of México
Authors: Juárez-Velázquez Rocio , Canto Patricia , Canto-Cetina Thelma , Rangel-Villalobos Hector , Rosas-Vargas Haydee , Rodríguez Maricela , Canizales-Quinteros Samuel , Velázquez Wong Ana Claudia , Ordoñez-Razo Rosa María , Vilchis-Dorantes Guadalupe , Coral-Vázquez Ramón Mauricio
Published: June 2013

Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235Tangiotensinogen (AGT), A222V5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1) polymorphismsin 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared usingχ2tests.

All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for theglutathione S-transferase P1polymorphism.

Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of theglutathione S-transferase P1and reduced occurrence of the 222A allele of the5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups.
Infection as a Risk Factor in the Pathogenesis of Primary Biliary Cirrhosis: Pros and Cons
Authors: Kumagi Teru , Abe Masanori , Ikeda Yoshiou , Hiasa Yoichi
Published: June 2013

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intrahepatic bile ducts that may eventually lead to cirrhosis and liver failure. Evidence suggests cardinal roles for both environmental factors and genetic susceptibility. Nevertheless, the absolute etiology of PBC is unclear, despite recent well-designed case-control studies that reported environmental risk factors, including infectious agents, for PBC. Of the reported infectious agents, some of them are not reproducible and remain controversial. However, infection is no doubt one of the major risks among the environmental factors. This is supported by the fact that infectious agents in autoimmune diseases express antigens resulting in molecular mimicry and xenobiotics that play a role in breaking tolerance. Taken together, recent findings from genome wide assays as well as novel animal models may enable us to better understand the mechanism of pathogenesis responsible for this disease.
Environmental Agents Involved in the Cause of Primary Biliary Cirrhosis
Authors: Kouroumalis Elias
Published: June 2013

Primary biliary cirrhosis (PBC) is an immune mediated chronic cholestatic liver disease with a slowly progressive course It is a universal disease with a reported latitudinal gradient in prevalence and incidence. The aetiology of primary biliary cirrhosis is still unknown. It is characterized by a 60% concordance in monozygotic twins and is considered an autoimmune disease because of several features common to other autoimmune conditions and the relatively homogeneous serological and biochemical features. However geoepidemiological and clinical studies strongly imply that environmental factors also play an important role. It is accepted that the disease is clearly the result of a combination of genetic and environmental factors. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics. This review will attempt to place such factors in perspective.
P2X7 Gene Polymorphisms and Risk Assessment for Pulmonary Tuberculosis in Asian Indians
Authors: Sambasivan Venkatasubramanian , Murthy Kolluri Janaki Rama , Reddy Ravindra , Vijayalakshimi Valluri , Hasan Qurratulain
Published: June 2013

Objective:Pulmonary tuberculosis (PTB) is a leading cause of morbidity and mortality. Macrophages play an important role in the immunopathogenesis of tuberculosis. Extracellular ATP induces macrophage bactericidal activity through activation of the purinergic P2X7 receptor. This case- control study assesses the association of −762 T/C, 1513A/C and 1729T/A P2X7 polymorphisms in patients with PTB and healthy controls to establish association if any with risk of developing the disease.

Materials and methods:The genotyping for P2X7 was carried out using PCR and RFLP analysis in 256 individuals, which included 156 active PTB patients and 100 age and sex, matched healthy volunteers with no clinical symptoms or family history of PTB as controls.

Results:A chi square test showed a significant difference between the PTB patient and controls for −762 C allele;p=0.0051 (OR 1.6972, CI 95% 1.1839 to 2.4332) and1729 T allele was found to be positively associated with the PTB;p< 0.0005 (OR-2.4623, CI 95% 1.6376 to 3.7022). 1513A/C polymorphism did not show any significant difference between the two groups.

Significance:The study revealed a significant association of P2X7-762C allele and P2X7 1729T allele receptor polymorphisms with PTB in Asian Indian population. The use of these alleles as biomarkers for identifying individuals at high risk of developing TB needs to be ascertained.
Expression and Significance of FXYD-3 Protein in Gastric Adenocarcinoma
Authors: Zhu Zhen-Long , Zhao Zeng-Ren , Zhang Yu , Yang Yan-Hong , Wang Zheng-Min , Cui Dong-Sheng , Wang Ming-Wei , Kleeff Jörg , Kayed Hany , Yan Bao-Yong , Sun Xiao-Feng
Published: June 2013

Objective:FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma.

Patients and methods:FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n= 29) and gastric adenocarcinoma (n= 51), obtained from surgical resection of gastric cancer patients.

Results:FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X2=13.210, p < 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X2= 5.765,p= 0.016). However, FXYD-3 expression was not correlated with patient’s gender, age, tumor size, lymph node status and histological grade (p> 0.05).

Conclosion:Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma.
Conflicting Views on the Molecular Structure of the Cancer Antigen CA125/MUC16
Authors: Bouanene Houda , Miled Abdelhédi
Published: June 2013

CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker.
On Chip Immuno-Affinity Profiling of Cancer- and Benign Hyperplasia-Associated Free Prostate Specific Antigen
Authors: Kosanovic Maja M. , Goc Sanja R. , Potpara Goran S. , Jankovic Miroslava M.
Published: June 2013

Prostate specific antigen (PSA) exhibits pronounced heterogeneity in both primary structure and glycan composition, resulting in the existence of different molecular forms. Investigation of PSA structure is a demanding task facing limitations due to inadequate sensitivity of analytical techniques and low concentrations of the different forms. This study aimed to profile free PSA (fPSA), especially lower molecular mass species lacking detailed classification, in normal seminal plasma and in sera from subjects with benign hyperplasia (BPH) or cancer of the prostate (PCa) as samples of known clinical relevance. fPSA forms were separated from complex proteomes on chips with immobilized anti-fPSA antibody followed by detection using surface-enhanced laser desorption/ionization time of flight mass spectrometry. At least 39 fPSA-immunoreactive species, ranging from 3–29 kDa were detected in seminal plasma. General fPSA profiles in seminal plasma and sera were similar, but differed in the abundance and presence of particular peaks/clusters of the lower molecular mass species. No striking difference in fPSA forms was observed between BPH and PCa samples, but some distinct peaks varied in intensity and frequency within or between groups. Obtained data verify fPSA heterogeneity that might be important for better exploration of all their molecular and marker potentials.
Fibronectin, Plasminogen Activator Inhibitor Type 1 (PAI-1) And Uterine Artery Doppler Velocimetry as Markers of Preeclampsia
Authors: Bodova Kristina Biskupska , Biringer Kamil , Dokus Karol , Ivankova Jela , Stasko Jan , Danko Jan
Published: June 2013

Objective: The purpose of this study was to examine plasma levels of fibronectin and plasminogen inhibitor type 1 (PAI-1), and alterations in uterine artery (UtA) waveforms throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy.

Material and methods: Blood samples were collected from 102 healthy, nulliparous women between the 24th and 26th gestational week. Preeclampsia developed in 13 patients; 89 normotensive control subjects were matched from the same cohort. Plasma samples were assayed for fibronectin and PAI-1 by enzyme-linked immunosorbent assay. Color pulsed Doppler examinations of UtA were performed after blood sampling. Trends were compared between two groups.

Results: Maternal plasma fibronectin and PAI-1 levels and average PI, RI and S/D ratios of patients with preeclampsia were significantly higher (p < 0.05). The best cut-off values for predicting preeclampsia of fibronectin, PAI-1, PI, RI, S/D ratio based on ROC curve analysis were 290 mg/ml, 77.3 ng/ml, 1,0615, 0.605 and 2,59 respectively. The areas under the curve equal to 0.705, 0.753, 0.689, 0.695 and 0.699 for fibronectin, PAI-1 and uterine artery Doppler PI, RI, S/D ratio were determined for the prediction of preeclampsia.

Conclusions: Fibronectin, PAI-1 and UtA Doppler are potentially useful predictors of preeclampsia. Maternal plasma PAI-1 combinated with fibronectin had the highest predictive values in our study.
Phosphodiesterase 4 D Gene Polymorphism in Relation to Intracranial and Extracranial Atherosclerosis in Ischemic Stroke
Authors: Kalita Jayantee , Somarajan Bindu I. , Kumar Bishwanath , Kumar Sunil , Mittal Balraj , Misra Usha K.
Published: June 2013

In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke.

Consecutive patients with MRI proven ischemic stroke undergoing MRA were included in this study. The severity of atherosclerotic stenosis on MRA was categorized into moderate 50%–80%, severe 80%–99%, and total occlusion 100% using NASCET criteria. The polymorphism in SNP 32, SNP 83 and SNP 87 of PDE4D gene was analyzed by PCR both in the patients and in 188 controls.

Among the 148 patients, MRA was abnormal in 77% patients; ECMRA in 53.8%, ICMRA in 66% and both were abnormal in 42% patients. The frequency of CC genotype of PDE4D83 was significantly higher in the patients with ischemic stroke compared to controls (OR 3.38, 95% CI 1.61–7.11,P= 0.001). The frequency of TT genotype of PDE4D87 was significantly higher ICMRA abnormalities (20%) compared to normal ICMRA (2%). The genotype and allele frequency of PDE4D83 and PDE4D32 were not significantly related to MRA abnormalities. The role of PDE4D87 in atherosclerosis needs confirmation in larger studies.
Genetic Markers for PTSD Risk and Resilience Among Survivors of the World Trade Center Attacks
Authors: Sarapas Casey , Cai Guiqing , Bierer Linda M. , Golier Julia A. , Galea Sandro , Ising Marcus , Rein Theo , Schmeidler James , Müller-Myhsok Bertram , Uhr Manfred , Holsboer Florian , Buxbaum Joseph D. , Yehuda Rachel
Published: June 2013

We have previously reported the differential expression of 17 probe sets in survivors of the 9/11 attacks with current posttraumatic stress disorder (PTSD) compared to similarly exposed survivors with no lifetime PTSD. The current study presents an expanded analysis of these subjects, including genotype at FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity. It includes data from additional subjects who developed PTSD following 9/11 but then recovered, distinguishing expression profiles associated with risk for developing PTSD, resilience, and symptom recovery. 40 Caucasians (20 with and 20 without PTSD, matched for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the 9/11 attacks from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained and genome-wide gene expression was analyzed. 25 probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal axis, signal transduction, or in brain and immune cell function. STAT5B, a direct inhibitor of GR, and nuclear factor I/A, both showed reduced expression in PTSD. Comparison of lifetime versus current PTSD identified overlapping genes with altered expression suggesting enduring markers, while some markers present only in current PTSD may reflect state measures. As a follow-up, direct comparisons of expression in current PTSD, lifetime-only PTSD, and control groups identified FKBP5 and MHC Class II as state markers, and also identified several trait markers. An analysis of indirect effects revealed that homozygosity for any of 4 PTSD risk-related polymorphisms at FKBP5 predicted FKBP5 expression, which mediated indirect effects of genotype on plasma cortisol and PTSD severity.
Endothelial Nitric Oxide Synthase Haplotypes Are Associated with Preeclampsia in Maya Mestizo Women
Authors: Díaz-Olguín Lizbeth , Coral-Vázquez Ramón Mauricio , Canto-Cetina Thelma , Canizales-Quinteros Samuel , Ramírez Regalado Belem , Fernández Genny , Canto Patricia
Published: June 2013

Preeclampsia is a specific disease of pregnancy and believed to have a genetic component. The aim of this study was to investigate if three polymorphisms ineNOSor their haplotypes are associated with preeclampsia in Maya mestizo women.

A case-control study was performed where 127 preeclamptic patients and 263 controls were included. Genotyped and haplotypes for the -768T→C, intron 4 variants, Glu298Asp ofeNOSwere determined by PCR and real-time PCR allelic discrimination. Logistic regression analysis with adjustment for age and body mass index (BMI) was used to test for associations between genotype and preeclampsia under recessive, codominant and dominant models. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlationr2, and haplotype analysis was conducted.

Women homozygous for the Asp298 allele showed an association of preeclampsia. In addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298 haplotype was significantly more frequent in preeclamptic patients than in controls (0.143 vs. 0.041, respectively; OR = 3.01; 95% CI = 1.74–5.23;P= 2.9 × 10−4).

Despite the Asp298 genotype in a recessive model associated with the presence of preeclampsia in Maya mestizo women, we believe that in this population the -786C-4b-Asp298 haplotype is a better genetic marker.
Effects of Six Functional SNPs on the Urinary 8-Isoprostane Level in a General Japanese Population; Shimane COHRE Study
Authors: Suyama Yoji , Matsuda Chikashi , Isomura Minoru , Hamano Tsuyoshi , Karino Kenji , Yamasaki Masayuki , Yamaguchi Shuhei , Shiwaku Kuninori , Masuda Junichi , Nabika Toru
Published: June 2013

Oxidative stress is an important risk factor for cardiovascular diseases. Although a variety of genetic factors are assumed to contribute to the regulation of oxidative stress, evidence in human populations is insufficient. In this study, we therefore evaluated the effects of six functional single-nucleotide polymorphisms (SNPs) on the oxidative stress under a cross-sectional study design. Participants of the health examination in two neighboring counties were recruited in a mountainous region of Shimane prefeture, Japan (n= 1092). As a marker for the oxidative stress, the urinary 8-isoprostane (IsoP) was measured by ELISA. The six SNPs were genotyped using the Taqman method. None of the SNPs showed a significant effect on the IsoP level. However, the Generalized Multiple Dimensionality Reduction (GMDR) method identified that the combination of the two SNPs, MTHFR C677T and eNOS T-786C, showed a significant effect on the IsoP level in this population. The linear regression analysis confirmed that the high risk genotype identified in the GMDR was an independent factor influencing the IsoP even after adjustment of confounding factors. This result suggested that GMDR analysis might be useful to identify concealed effects of combined SNPs.
Prognostic Markers in Patients with Cirrhosis and Portal Hypertension Who Have Not Bled
Authors: Poca Maria , Puente Angela , Graupera Isabel , Villanueva Càndid
Published: June 2013

Prognostic markers of compensated cirrhosis should mainly investigate factors involved with progression to decompensation because death in cirrhosis is related with decompensation. Portal hypertension plays a crucial role in the pathophysiology of most complications of cirrhosis. Accordingly, HVPGmonitoring has strong prognostic value. An HVPG ≥ 10 mmHg determines a significantly higher risk of developing decompensation. Esophageal varices also can develop when the HVPG is ≥ 10 mmHg, although an HVPG ≥ 12 mmHg is required for variceal bleeding to occur. Monitoring the changes induced by the treatment of portal hypertension on HVPG, provides strong prognostic information. In compensated cirrhosis hemodynamic response is appropriate when the HVPG decreased to <10 mmHg or by > 10% from baseline, because the incidence of complications such as bleeding or ascites significantly decrease when these targets are achieved. Whether serum markers, such as the FibroTest, they, may be valuable to predict decompensation should be established. Transient Elastography is a promising technique that has shown an excellent accuracy to detect severe portal hypertension. However, whether it can adequately determine clinically significant portal hypertension, and risk of developing varices and decompensation, should be established. Magnetic Resonance Elastography is also promising.
Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis
Authors: Dalgic Nazan , Tekin Deniz , Kayaalti Zeliha , Cakir Erkan , Soylemezoglu Tulin , Sancar Mesut
Published: June 2013

Objectives:Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population.

Methods:The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects.

Results:We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p> 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98,p= 0.007).

Conclusions:Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.
Psoriasis-Associated Genetic Polymorphism in North Indian Population in the CCHCR1 Gene and in a Genomic Segment Flanking the HLA-C Region
Authors: Gandhi G. , Buttar B. Singh , Albert L. , Hasan Q. , Aggarwal R. K.
Published: June 2013

Psoriasis is a common, chronic, recurrent, inflammatory, hyper proliferative disorder of the skin, which has a relatively high prevalence in the general population (0.6–4.8%). Linkage and association analyses in various populations have revealed a major locus for psoriasis susceptibility, PSORS1, at 6p21.3. Association of the disease with human leukocyte antigen (HLA) Cw6, corneodesmosin (CDSN) and the coiled-coil alpha-helical rod protein-1 (CCHCR1) has also been reported. Though the PSORS1 locus accounts for 30–50% of familial psoriasis in various global population groups, yet no studies have been published from the North Indian population. Some of the SNPs in HLA-C and CCHCR1 genes have been reported as markers for disease susceptibility. Therefore in the present study, DNA samples from psoriasis patients from North India were genotyped for polymorphisms in CCHCR1 and HLA-C genes. The allele frequencies were calculated for patients and controls, and were compared for odds ratio and confidence interval values. SNPn.7*22222 (rs12208888), SNPn.7*22333 (rs12216025), SNPn.9*24118 (rs10456057), CCHCR1_386 (rs130065), CCHCR1_404 (rs130076) and CCHCR1_1364 (rs130071) were found to be significant in psoriasis patients. Linkage disequilibrium analysis revealed two haplotypes (rs12208888,rs2844608,rs12216025,rs10456057,rs130065,rs130066,rs130068,rs130269,andrs12208888,rs2844608,rs12216025,rs130076,rs130066,rs130068,rs130269,rs130071) as highly susceptible haplotypes for psoriasis in the cohort studied. Preliminary analysis of the data also suggests the possibilities of ethnic group specific disease related polymorphisms, pending validation in future studies.
Detection of Autoantibodies Against Glycosylated-DNA in Diabetic Subjects: Its Possible Correlation with HbA1C
Authors: Ahmad Jamal , Gupta Anuj , Alam Khursheed , Farooqui Khalid Jamal
Published: June 2013

Aims: The vascular tissues have a long memory of their previous glycemic control and intervention studies have demonstrated that microvascular complications are highly correlated with mean glycemic control as measured by glycolated hemoglobin A1C (HbA1c). The present study was carried out to evaluate the autoantibodies against glycosylated DNA (DNAAGEs) in diabetic sera to see if the level of HbA1c has correlation with the activity of DNA-AGEs, another marker of chronic glycemia.

Methods: Glucose-6-phosphate induced glycosylation of native DNA was studied in 150 diabetic sera (T1DM = 9, T2DM = 141) by spectroscopic techniques (UV and fluorescence) and agarose gel electrophoresis. Direct binding and inhibition enzyme immunoassays were carried out to evaluate binding and specificity of anti-glycated-DNA autoantibodies (anti-DNA-AGE autoantibodies) in sera of diabetes patients. A quantitative estimation of HbA1cwas carried out in normal and diabetes sera.

Results: Anti-DNA-AGEs autoantibodies in 55% of diabetic sera (85/150) showed more binding with glycated-DNA compared to native DNA which was subjected to inhibition ELISA indicating true interaction of these autoantibodies in diabetes with glycated DNA. Higher binding with glycosylated-DNA against native-DNA was observed in subjects with HbA1c of 9.8 ± 3.3% compared to those with HbA1c of 7.7 ± 1.7% (p < 0.001). Linear correlation analysis showed that mean absorbance difference was significantly related to HbA1c (r= 0.486, p < 0.001), nephropathy (r= 0.239, p < 0.003), retinopathy (r= 0.165, p < 0.05).

Conclusions: Autoantibodies against glycosylated DNA were correlated with HbA1cand microvascular complications and may be useful as another biomarker for assessment of chronic glycemia.