shlokn/autogkb huggingface dataset:
Article: The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients
Gene: POR
Variant/haplotype: rs1057868
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased metabolism of tacrolimus in people with Kidney Transplantation as compared to allele C.
Notes: A single steady-state concentration of tacrolimus was collected for each patient 2-7 wks post-transplant and compared to dose of tacrolimus administered to patients at Oslo University Hospital. Reported concentrations are "steady-state dose-adjusted concentration" of tacrolimus. Steady-state is defined as at least 3 days after last dose adjustment for Tac and 4 days for cyclosporine.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: CYP3A4
Variant/haplotype: rs28371759
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AG is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype AA.
Notes: from TABLE 4 Ticagrelor pharmacokinetic parameters based on genotypes without statistical significance and TABLE 5; AR-C124910XX pharmacokinetic parameters based on genotypes without statistical significance
Article: Pharmacogenetic Predictors of Adverse Events and Response to Chemotherapy in Metastatic Colorectal Cancer: Results From North American Gastrointestinal Intergroup Trial N9741
Gene: UGT1A1
Variant/haplotype: rs10929302
Drug(s): fluorouracil, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to fluorouracil, irinotecan or oxaliplatin in people with Colorectal Neoplasms as compared to genotypes AG + GG.
Notes: Patients were taking either IFL (irinotecan + fluorouracil + leucovorin; n=114), FOLFOX (fluorouracil + oxaliplatin + leucovorin; n=299) or IROX (irinotecan + oxaliplatin; n=107). No significant association was seen between this variant and confirmed response rate in any of the treatment groups OR all treatment groups considered together. Significance level was set at 0.01. rs10929302 is reported as UGT1A1*93 (UGT1A1 *93/*93 is not associated with response to fluorouracil, irinotecan or oxaliplatin in people with Colorectal Neoplasms as compared to UGT1A1 *1/*1 + *1/*93).
Article: Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia
Gene: CYP1A2
Variant/haplotype: rs762551
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased exposure to clozapine in people with Schizophrenia and Tobacco Use Disorder as compared to genotypes AC + CC.
Notes: "A significant difference in pharmacokinetic parameters was associated with the polymorphism of CYP1A2 gene encoding the main enzyme related to the metabolism of CLZ. Patient smokers (>7 cigarettes/day) with the *1F/*1F genotype for the CYP1A2 gene had significant differences according to CLZ plasma levels and C/D CLZ (p = 0.029 and p = 0.034, respectively) versus *1/*1F and *1/*1 genotypes. Patients with *1F/*1F (n = 49) showed lower values with significant differences between the smoker (n = 20) and non-smoker (n = 29) population according to CLZ dose, C/D total, C/D CLZ, and C/D NCLZ (p = 0.002, p = 0.035, p = 0.046, and p = 0.032, respectively)." Annotation done on rs762551 (-163C>A). PharmVar released an updated CYP1A2 nomenclature 12/2024. At this point, -163 C>A was included in 26 core alleles with *30 being the SNP by itself. The 25 other core alleles include the -163 C>A SNP in addition to amino acid changes.
Article: Cytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639G<A) gene polymorphisms & their effect on acenocoumarol dose in patients with mechanical heart valve replacement
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): acenocoumarol
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *3 is associated with decreased dose of acenocoumarol as compared to CYP2C9 *1.
Notes: The CYP2C9*2, *3 and VKORC1 rs9923231 are analyzed together. Patients carrying any of the variant alleles was 34% among those receiving a low dose of =20 mg/wk while it was 13.8 per cent in those receiving >20 mg/wk (P=0.014).
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: UGGT2
Variant/haplotype: rs9590353
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele T.
Notes: The SNP was discovered in two independent cohorts, although no SNPs reached genome wide significance. The authors then considered P<1 x10^-5 as a threshold for significance (based on the results from a Q-Q plot distribution reference line). Using this revised threshold the authors reported that this SNP was associated with a lower decrease in diastolic blood pressure after hydrochlorothiazide treatment.
Article: Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): apixaban
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AG are not associated with clearance of apixaban in people with Atrial Fibrillation as compared to genotype GG.
Article: In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles
Gene: CYP2D6
Variant/haplotype: CYP2D6 intermediate metabolizers
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 intermediate metabolizer is associated with decreased concentrations of endoxifen in women with Breast Neoplasms as compared to CYP2D6 normal metabolizer.
Notes: The patients of the cohort (83% White, 15% Black) were genotype with AmpliChip CYP450 test. The variations used to define the star alleles are not reported. The diplotypes of the patients are not reported. The alleles found in the cohort are not explicit reported but graphic 3 shows *1, *2, *35, *9, *10, *17, *29, and *41. The study included UMs and PM but no CYP2D6 star allele is reported for those phenotypes. *1, *2, *35 are grouped as active alleles and any combination of these defines the extensive metabolizer. *9, *10, *17, *29, and *41 are grouped as reduced function alleles. The article subgroups the IMs into EM/IM, EM/PM, IM/IM, IM/PM.
Article: Genome-wide association study of patient and clinician rated global impression severity during antipsychotic treatment
Gene: PPA2
Variant/haplotype: rs2636719
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to risperidone in people with Schizophrenia as compared to allele C.
Notes: The number of G alleles present in a patient was positively associated with CGI-S score. Please note that this variant is in high linkage disequilibrium with rs2636697.
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: SLC6A2
Variant/haplotype: rs5569
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.
Notes: Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).
Article: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): selumetinib
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of selumetinib in healthy individuals as compared to allele G.
Notes: Not associated with AUC, AUC0-12 when allele was assessed within ethnic groups (Asian, White, Black) and when all ethnic groups were pooled together. Only P-values for AUC presented here.
Article: Impact of Single Nucleotide Polymorphisms on Plasma Concentrations of Efavirenz and Lopinavir/ritonavir in Chinese Children Infected with the Human Immunodeficiency Virus
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CC + CT are not associated with concentrations of efavirenz in children with HIV Infections as compared to genotype TT.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: HTR2A
Variant/haplotype: rs6311
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to risperidone in people with Schizophrenia as compared to allele T.
Article: Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome‐Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2
Variant/haplotype: rs28845026
Drug(s): anastrozole
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased concentrations of anastrozole in women with Breast Neoplasms as compared to allele C.
Notes: The minor allele of this variant was associated with increased plasma concentrations of anastrozole in postmenopausal women with ER+ breast cancer.
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: ADGRL3
Variant/haplotype: rs6551665
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.
Notes: Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: CHURC1
Variant/haplotype: rs4902333
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele T 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: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *1/*3 + *2/*2 + *2/*3 + *3/*3 are not associated with dose of methadone in people with Opioid-Related Disorders as compared to CYP2C9 *1/*1 + *1/*2.
Notes: No significant difference in methadone dose between genotypes. No details about which specific variants/alleles were tested for.
Article: Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Variant/haplotype: rs5836788
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele del is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C.
Article: Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation
Gene: CYP3A7
Variant/haplotype: CYP3A7*1A, CYP3A7*1C
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A7 *1A/*1A is associated with decreased concentrations of tacrolimus in children with Kidney Transplantation as compared to CYP3A7 *1A/*1C + *1C/*1C.
Notes: Dose-corrected tacrolimus exposure (AUC0-12/doseBW).
Article: Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in post-menopausal patients with breast cancer
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): exemestane
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A4 *1/*22 is associated with increased concentrations of exemestane in women with Breast Neoplasms as compared to CYP3A4 *1/*1.
Notes: The *22 allele was associated with a 54% greater exemestane concentration, and remained significant after adjustment for covariates.
Article: Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia
Gene: CYP1A2
Variant/haplotype: rs762551
Drug(s): clozapine
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased clinical benefit to clozapine in people with Schizophrenia as compared to genotypes AC + CC.
Notes: CYP1A2 *1F/*1F is associated with decreased clinical benefit to clozapine in people with Schizophrenia. "CYP1A2 rs7625521 also demonstrated a significant association with the Brief Negative Symptom Scale (BNSS) expression factor subscale (p = 0.007) between *1F and *1 allele. Patients with the *1F/*1F genotype were associated with a significant worsening of expression factor subscale (p = 0.037). No association with BNSS overall score, BNSS Motivation and Pleasure Factor score, PANSS-positive score, Wellbeing (SWEMWBS) score, or Genal functioning (GAF) score." "...impaired emotional expressivity is more prominently observed in patients carrying the *1F/*1F genotype as compared to patients with at least one wild type allele for CYP1A2 (*1 allele), potentially associated with a reduction in metabolism, leading to a poorer response." The quote has a typo that is in the paper, the correct rs number should be rs762551. Annotation done on rs762551 (-163C>A). PharmVar released an updated CYP1A2 nomenclature 12/2024. At this point, -163 C>A was included in 26 core alleles with *30 being the SNP by itself. The 25 other core alleles include the -163 C>A SNP in addition to amino acid changes.
Article: KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment
Gene: KIF6
Variant/haplotype: rs20455
Drug(s): atorvastatin, simvastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to atorvastatin or simvastatin in people with Hypercholesterolemia as compared to genotype AA.
Notes: Please note that alleles have been complemented to the positive strand.
Article: G-Protein-Coupled Receptor Kinase 4 Polymorphisms and Blood Pressure Response to Metoprolol Among African Americans: Sex-Specificity and Interactions
Gene: GRK4
Variant/haplotype: rs1801058
Drug(s): metoprolol
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is not associated with decreased response to metoprolol in men with hypertensive nephrosclerosis as compared to genotype CC.
Notes: Note; TT (V486) homozygotes were excluded. Response was measured by time to reach a mean arterial pressure of < or = 107 mm Hg.
Article: Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation
Gene: GSTM3
Variant/haplotype: rs7483
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased concentrations of tacrolimus in people with Liver transplantation as compared to genotypes CC + CT.
Notes: Alleles complemented. This was seen only for donor not recipient: For donor "Tac C/D ratios of donor GSTM3 rs7483 AA genotype were 231.0 ± 164.9, 127.3 ± 73.6, 120.4 ± 82.4 and 116.1 ± 71.1 at weeks 1, 2, 3 and 4 respectively. For AG and GG genotype carriers, the corresponding Tac C/D ratios at each time point were 328.2 ± 243.6, 195.1 ± 146.6, 213.4 ± 219.6 and 235.20 ± 180.3. The differences were significant (p = 0.035, 0.010, 0.035, 0.002, respectively)."
Article: Novel and replicated clinical and genetic risk factors for toxicity from high-dose methotrexate in pediatric acute lymphoblastic leukemia
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele G is associated with increased clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele A.
Notes: "The G allele of rs2306283, which causes a missense mutation in SLCO1B1, demonstrated a; decreased risk for prolonged clearance"
Article: The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men
Gene: SLCO1B1
Variant/haplotype: rs11045819
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of lopinavir or ritonavir in men with HIV Infections as compared to allele C.
Notes: No significant association between this variant and trough concentrations of lopinavir or ritonavir in HIV patients treated with lopinavir/ritonavir. Variant referred to in the paper as 463C>A.
Article: Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin
Gene: SP1
Variant/haplotype: rs784888
Drug(s): metformin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele G is associated with decreased clearance of metformin in healthy individuals as compared to allele C.
Article: Impact of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir in patients with pancreatic cancer
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): nelfinavir
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 is associated with increased concentrations of nelfinavir in people with Pancreatic Neoplasms as compared to CYP2C19 *1/*1.
Notes: All patients were genotyped for CYP2C19 by RFLP analysis. Female and male patients were initially administered 750 or 900 mg/m2 gemcitabine IV over 30 min, 50 mg/m2 leucovorin IV over 30 min, and 2700 mg/m2 5-FU IV over 24 hours on day 1 weekly for 2 of 3 weeks for three cycles (day 1-63). Oral nelfinavir was given at 625 mg or 1250 mg twice daily for 3 weeks starting 2 weeks prior to initiation of radiation (days 56-75). 625 mg is better tolerated and preferred by patients. 1250 mg is the standard dose of nelfinavir when used to treat HIV patients. Differences in Cmax (mean) between genotype groups was only seen in the 1250 mg dose and not in the 650 mg dose. The AUC (0-12), terminal half-life, total body clearance (CLT/F) and apparent volume of distribution of nelfinavir (VD/F)did not significantly different between CYP2C19 genotype group.
Article: Pharmacogenetics and Pharmacokinetics of Tamoxifen in a Zimbabwean breast cancer cohort
Gene: CYP2D6
Variant/haplotype: CYP2D6 intermediate metabolizer
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 intermediate metabolizer is associated with decreased concentrations of endoxifen in people with Breast Neoplasms as compared to CYP2D6 normal metabolizer.
Notes: "The common phenotype; group was that of the normal metabolizers (NM), which was 67.5%. However, intermediate; metabolizers (IMs) had quite a significant frequency of 27.5%, while the frequency of; ultrarapid metabolizers (UMs) was 5%. There were no CYP2D6 poor metabolizers in this; study." Authors used CPIC phenotype classifications. "55.0% were post-menopausal women" "All the recruited; participants were female except 1 who was male." "Most of the breast cancer patients had a late diagnosis with at least; stage 3A breast cancer at diagnosis (64.9%)"
Article: Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): 4-hydroxytamoxifen, endoxifen, N-desmethyltamoxifen, tamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C9 *3 is not associated with concentrations of 4-hydroxytamoxifen, endoxifen, n-desmethyltamoxifen and tamoxifen in women with Breast Neoplasms as compared to CYP2C9 *1.
Notes: Patients (pre- (83%) and postmenopausal (17%)) with ER and/or PR positive breast tumors, which received 20 mg tamoxifen daily. Patients taking CYP2D6 inhibitors were excluded. DNA extracted from blood.
Article: Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together
Gene: CYP2D6
Variant/haplotype: CYP2D6*10
Drug(s): atomoxetine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *10/*10 (assigned as intermediate metabolizer phenotype) is associated with increased exposure to atomoxetine in children with Attention Deficit Disorder with Hyperactivity as compared to CYP2D6 normal metabolizer.
Notes: "CYP2D6 IMs exhibited significantly higher atomoxetine C/D values than EMs under the three dosing regimens" The regimens were qm (once morning), bid (twice daily) and qn (once nightly). Study measured CYP2D6*2, CYP2D6*10, and CYP2D6*14 and grouped *10/*10 as intermediate. There was only one PM that was excluded from analysis.
Article: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs17179108
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: yes
Association: Genotype CT is associated with increased response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). The CT genotype was associated with improved DFS, but not OS.
Article: Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters
Gene: GGCX
Variant/haplotype: rs12714145
Drug(s): phenprocoumon
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Genotype CC is not associated with increased dose of phenprocoumon as compared to genotypes CT + TT.
Notes: Daily dose of phenprocoumon is not significantly associated with this SNP. Daily dose is negatively correlated with age. This study published an algorithm for daily dose that includes height, although height was not significant in univariate analysis. This SNP is also not significantly associated with phenprocoumon concentration.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Gene: CYP3A43
Variant/haplotype: rs17161981
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele G.
Article: Influence of CYP450 Enzymes and ABCB1 Polymorphisms on Clopidogrel Response in Moroccan Patients with Acute Coronary Syndromes
Gene: CYP2C19
Variant/haplotype: CYP2C19 normal metabolizer
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 normal metabolizer is not associated with increased response to clopidogrel in people with Acute coronary syndrome as compared to CYP2C19 rapid metabolizer.
Notes: "Patients were subdivided into clopidogrel responder (PRU≤208) and clopidogrel non-responder group (PRU>208), 19 patients (34.55%) were clopidogrel non-responders, whereas 36 patients (65.45%) were clopidogrel responders. " "The tested alleles CYP2C9*3, Cyp2C19*2, Cyp2C19*3, CYP3A4*22, and CYP3A5*2 were not found in our study population"