shlokn/autogkb huggingface dataset:
Article: Gene‐Wide Tagging Study of the Association Between KCNT1 Polymorphisms and the Susceptibility and Efficacy of Genetic Generalized Epilepsy in Chinese Population
Gene: KCNT1
Variant/haplotype: rs487750
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to antiepileptics in people with Epilepsy, Generalized as compared to allele T.
Notes: No significant differences in genotype frequencies were seen between patients who were responsive to antiepileptic drugs (n=279; those who had not experienced any type of seizure for a minimum of 1 year after receiving antiepileptic drugs) and patients who were resistant to antiepileptic drugs (n=204; those who had at least four seizures during the previous year while trying at least three antiepileptic medications at the maximal tolerated doses). Please note alleles have been complemented to the plus chromosomal strand.
Article: Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test
Gene: ATF2
Variant/haplotype: rs268214
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to fentanyl in people with Pain, Postoperative as compared to allele T.
Article: Influence of Genetic Variants on Steady-State Etonogestrel Concentrations Among Contraceptive Implant Users
Gene: PGR
Variant/haplotype: rs537681
Drug(s): etonogestrel
Phenotype category: Efficacy, Metabolism/PK
Significant: no
Association: Genotypes CT + TT is associated with decreased steady-state concentration of etonogestrel in women as compared to genotype CC.
Notes: "11.7% (31/266) of carriers for rs537681 had serum etonogestrel concentrations that fell below 90 pg/mL" (the level for suppression of ovulation) in contraceptive implant users which may theoretically put them at risk for contraceptive failure. Corrected P-value cutoff of 5.0E-4 was not met.
Article: Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment
Gene: CYP1A2
Variant/haplotype: CYP1A2 low activity
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP1A2 low activity is not associated with trough concentration of methadone as compared to CYP1A2 high activity.
Notes: CYP1A2 phenotype, as assessed by caffeine metabolism did not significantly contribute to variance in methadone trough plasma concentrations.
Article: Association between Genetic Polymorphism of SCN1A, GABRA1 and ABCB1 and Drug Responsiveness in Vietnamese Epileptic Children
Gene: SCN1A
Variant/haplotype: rs2298771
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased resistance to antiepileptics in children with Epilepsy as compared to genotype TT.
Notes: Alleles complemented. Specific drugs not specified. "For rs2298771 G > A (p.Thr1067Ala), this is a variant in the coding region of the SCN1A gene. We found that the heterozygous genotype GA is a risk factor of DRE. The recessive model also showed that carriers of the G allele (GG + GA) were at higher risk of being drug-resistant. There were limited individuals with the GG genotype in both studies groups, therefore no statistical significance was found regarding the homozygous GG genotype among the two groups. "
Article: Influence of FMO3 and CYP3A4 Polymorphisms on the Pharmacokinetics of Teneligliptin in Humans
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): teneligliptin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with decreased concentrations of teneligliptin in men as compared to genotype CC.
Notes: Alleles complemented to plus chromosomal strand. Significant only for Cmax, not for AUC or CL/F.
Article: Influence of OATP1B1 and BCRP polymorphisms on the pharmacokinetics and pharmacodynamics of rosuvastatin in elderly and young Korean subjects
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): rosuvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT are associated with increased concentrations of rosuvastatin as compared to genotype GG.
Notes: The exposure to rosuvastatin increased by 44% in young subjects (p = 0.0021) with BCRP intermediate function (IF) and by 35% and 59% (p > 0.05 for both) in elderly subjects with BCRP IF and low function. The ABCG2 421C > A polymorphism was identified as a more important determinant than the SLCO1B1 521T > C polymorphism in both elderly and young subjects.
Article: ABCB1, CYP2B6, and CYP3A4 Genetic Polymorphisms do not Affect Methadone Maintenance Treatment in HCV-positive Patients
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of methadone in men with Heroin Dependence as compared to allele C.
Article: Novel genomic variants influencing methotrexate delayed clearance in pediatric patients with acute lymphoblastic leukemia
Gene: ENG
Variant/haplotype: rs1800956
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele G is associated with decreased clearance of methotrexate in children with Acute lymphoblastic leukemia as compared to allele C.
Notes: "All eight patients with ENG rs1800956 exhibited delayed MTX clearance. " "Case (MTX, delayed clearance) was defined as serum MTX, level (μmol/L) at 24 h ≥ 15 or 48 h ≥ 1.5 or 72 h ≥ 0.15 or 168 h ≥ 0.1, otherwise defined as control."
Article: Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy
Gene: SLC22A1
Variant/haplotype: rs2282143
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotypes CT + TT.
Notes: This genotype was not significantly with associated with likelihood of achieving a major molecular response (MMR) within 12 months. MMR was classified based on BCR-ABL to control gene transcript ratios, expressed on the International Scale; MMR was a ratio <= 0.1%.
Article: Impact of Genetic Variants on Pregabalin Pharmacokinetics and Safety
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): pregabalin
Phenotype category: Metabolism/PK
Significant: yes
Association: NAT2 slow acetylator is associated with increased exposure to pregabalin in healthy individuals as compared to NAT2 intermediate acetylator and rapid acetylator.
Notes: " In this study,; NAT2 SAs showed a 16–18% increase in exposure compared to IAs and NAs. The observed; variations in t1/2 and Cl/F appear consistent, as NAT2 SAs exhibited a 25% higher t1/2 as; compared with NAT2 IAs and 58% higher compared to NAT2 NAs. Our findings suggest; that NAT2 could be partially responsible for the minor proportion of pregabalin metabolism." Alleles measured (table 5) were *5 rs1801280 (T>C), *6 rs1799930 (G>A) and *7 rs1799931 (G>A).
Article: Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota
Gene: CYP2D6
Variant/haplotype: rs35742686
Drug(s): hydrocodone, oxycodone
Phenotype category: Efficacy
Significant: yes
Association: Allele DELT is associated with increased clinical benefit to hydrocodone or oxycodone in people with Pain as compared to allele T.
Notes: variant is described as C "protective" against poor pain control compared to CT.
Article: Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to clopidogrel in people with Coronary Artery Disease as compared to genotypes AG + GG.
Notes: "CYP2C19*2 AA carriers presented significantly lower mean PAIR% values (59.60 ± 26.07) than CYP2C19*2 GA carriers (74.84 ± 25.09) (p = 0.015). Our results also indicated that CYP2C19*2 AA carriers presented significantly lower mean PAIR% values (59.60 ± 26.07) than CYP2C19*2 GG carriers (77.63 ± 23.69) (p = 0.003) (Figure 1D)."
Article: PTPRD gene associated with blood pressure response to atenolol and resistant hypertension
Variant/haplotype: rs12346562
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AC is associated with decreased response to hydrochlorothiazide in people with Hypertension as compared to genotype CC.
Notes: The A allele of SNP rs12346562 was associated with better DBP response to atenolol, but with less pronounced response to hydrochlorothiazide. White participants with rs12346562 AA, AC, and CC genotypes had mean DBP responses of -3.8,-3.8, and -5.6 mmHg to atenolol (P=0.0018, b=1.55 mmHg; per A allele).
Article: Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype TT is associated with increased concentrations of efavirenz in people with Hepatitis B and HIV Infections as compared to genotypes GG + GT.
Notes: A systematic review. The authors only state that in the reviewed studies, patients with the slow metabolizer phenotype (associated with the TT genotype) had increased concentrations of efavirenz.
Article: SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours
Gene: NT5C3A
Variant/haplotype: rs6946062
Drug(s): gemcitabine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with metabolism of gemcitabine as compared to genotypes CC + CT.
Notes: Gemcitabine, dFdCTP, and dFdU plasma concentrations were measured before (5, 15, 30, 45 min) and after gemcitabine infusion (1, 1.25, 1.5, 2, 6, 24, 48, 72 hrs). Population pharmacokinetic analysis of gemcitabine and metabolites (dFdU, dFdCTP) were performed by non-linear mixed effects modeling. rs6946062 is not associated with metabolism of gemcitabine.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with exposure to lopinavir or ritonavir in children with HIV Infections as compared to allele A.
Notes: No association between this variant and AUC0-12 of lopinavir or ritonavir in patients treated with lopinavir/ritonavir. Variant referred to in the paper as A388G.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: ZNF565
Variant/haplotype: rs4805162
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Variant/haplotype: rs4680
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele G.
Notes: Methadone maintenance dose was not associated with genotype of the SNP but it was correlated to the highest dose ever used. Multiple doses versus single dose, body weight, history of cocaine dependence and ethnicity (Asian>Caucasian>African) were independently associated with methadone dose in multiple regression analysis.
Article: Impact of Single Nucleotide Polymorphisms on Plasma Concentrations of Efavirenz and Lopinavir/ritonavir in Chinese Children Infected with the Human Immunodeficiency Virus
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): lopinavir
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AG are not associated with concentrations of lopinavir in children with HIV Infections as compared to genotype GG.
Article: Influences of Organic Cation Transporter Polymorphisms on the Population Pharmacokinetics of Metformin in Healthy Subjects
Gene: SLC22A1
Variant/haplotype: rs2282143
Drug(s): metformin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased clearance of metformin in healthy individuals as compared to genotypes CT + TT.
Notes: Healthy individuals with the CC genotype had decreased area under the serum concentration-time curve from zero to infinity (AUCinf) of metformin as compared to those with the CT or TT genotype. However, no significant association was seen for peak concentration (Cmax) of metformin.
Article: Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): sunitinib
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to sunitinib in people with Carcinoma, Renal Cell as compared to genotypes GG + GT.
Notes: The genotype was not associated with progression free survival, or overall survival, or clinical benefit. Clinical benefit was defined as either partial response or stable disease. Please note, alleles have been complemented to the + chromosomal strand.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*55
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2A6 *55 is associated with decreased metabolism of nicotine as compared to CYP2A6 *1.
Notes: Assigned as decreased function following in vitro assessments, in vivo associations and variant construct functional assignments. Variant referred to as rs114558780 in the paper.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs16855294
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele C.
Notes: The allele did not reach genome wide significance in the discovery or replication cohorts. GWA analyses were performed for two phenotypes: ‘% change in HRSD-17 score’ (% HRSD defined as the change in HRSD-17 score divided by the baseline score) and ‘response’ (defined as greater than or equal to 50% reduction in HRSD-17 score from baseline to 4-week visit).
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: NFIB
Variant/haplotype: rs7858
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients
Gene: VEGFA
Variant/haplotype: rs833068
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bevacizumab in women with Breast Neoplasms as compared to allele G.
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: DRD4
Variant/haplotype: rs2133251840
Drug(s): clozapine
Phenotype category: Efficacy
Significant: yes
Association: Allele del is associated with increased clinical benefit to clozapine in people with Schizophrenia or Psychotic Disorder as compared to allele GA.
Notes: Alleles complemented. Table does not state which allele or direction of effect for these SNPs, so assuming minor allele and benefit, PANSS beta is in Table negative. "four SNPs in two genes were significantly associated with the total PANSS score: rs7787082 and rs10248420 in ABCB1 and rs2133251840 and rs762502 in DRD4 (Table 5). Among these, only one SNP in DRD4 (rs2133251840) resulted in different total PANSS scores at visits 3 and 4 according to its genotype"
Article: Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients
Gene: CYP2C9
Variant/haplotype: rs56165452
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype CT is associated with decreased dose of warfarin as compared to genotype TT.
Notes: This SNP defines CYP2C9*4. CYP2C9 *2,*3,*4,*5,*8 were grouped into three groups for testing: *1/*1 vs. *1/*2 + *1/*3 + *1/*4 + *1/*5 + *1/*8 vs *2/*2 + *2/*3 + *3/*3 + *5/*5. People having one or two variant alleles had lower dose requirements than people who were *1/*1.
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: PLAGL1
Variant/haplotype: rs3819811
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with response to olanzapine in people with Schizophrenia.
Notes: as measured by changes in PANSS-T (positive and negative syndrome scale total score), using a mixed model repeated measures approach. Examined 6789 SNPs - p-value of p< or equal to 5x10-4 was considered significant. It was unclear whether the allele was associated with an increased or decreased response to drug.
Article: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: ABCG2
Variant/haplotype: rs2231137
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.
Notes: Please note: alleles have been complemented to the + chromosomal strand.
Article: An Investigational Study on the Role of CYP2D6, CYP3A4 and UGTs Genetic Variation on Fesoterodine Pharmacokinetics in Young Healthy Volunteers
Gene: CES1
Variant/haplotype: rs2244613
Drug(s): fesoterodine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype GT is associated with decreased half-life time of fesoterodine in healthy individuals as compared to genotype TT.
Notes: "subjects with the CES1 rs2244613 C/A genotype were associated with a lower T1/2 compared to those with the A/A genotype (puv = 0.026) (Table 3). However, this association was not maintained in the multivariate analysis."
Article: Warfarin dose requirements in a patient with the CYP2C9*14 allele
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*14
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: CYP2C9 *1/*14 is associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: This patient also carries the warfarin insensitive VKORC1 -1639GG and CYP4F2 433Met/Met genotypes.
Article: IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased exposure to tacrolimus in people with Kidney Transplantation as compared to genotypes CT + TT.
Notes: This association was seen for time 7, 30, and 90 days after transplantation. Exposure to CC was higher than CT, which was higher than TT.
Article: Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder
Gene: ADH1B
Variant/haplotype: rs1229984
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to naltrexone in men with Alcoholism as compared to allele C.
Notes: Please note that alleles have been complemented to the positive strand. The T allele is also referred to as the ADH1B*2 allele in the paper.
Article: Effects of genetic variants of organic cation transporters on metformin response in newly diagnosed patients with type 2 diabetes
Gene: CBARP, STK11
Variant/haplotype: rs2301759
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with decreased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes CC + CT.
Notes: "Only STK11 (rs2301759) significantly affected metformin response among patients. T/T was the most frequent genotype (85%) in the inadequate-response group (P = .021). Other SNPs (rs4621031, rs34399035, rs1800058, and rs11212617) had no significant impact on metformin response. "
Article: COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and Methamphetamine Dependence Treatment Response: Preliminary Investigation
Gene: COMT
Variant/haplotype: rs4680
Drug(s): modafinil
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to modafinil in people with methamphetamine dependence as compared to genotypes AA + AG.
Notes: Hispanic subjects with the GG genotype had significantly higher Treatment Effectiveness Scores when treated with modafinil compared to placebo. This significant association was not seen when comparing modafinil treatment against placebo in subject with the AA or AG genotypes.
Article: Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population
Gene: RELN
Variant/haplotype: rs362813
Drug(s): aripiprazole, olanzapine, perphenazine, quetiapine, risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to aripiprazole, olanzapine, perphenazine, quetiapine or risperidone in people with Schizophrenia as compared to allele T.
Notes: Response was assessed by changes in PANSS score. A reduction of 50% or more in PANSS score was classified as a good response.