shlokn/autogkb huggingface dataset:
Article: A Markov Chain Model to Evaluate the Effect of CYP3A5 and ABCB1 Polymorphisms on Adverse Events Associated with Tacrolimus in Pediatric Renal Transplantation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *3/*3 is associated with decreased metabolism of tacrolimus in children with Kidney Transplantation as compared to CYP3A5 *1/*1 + *1/*3.
Notes: Patients who were CYP3A5 nonexpressors (CYP3A5 *3/*3; CC) had increased dose-normalized by body weight concentration of tacrolimus as compared to those who were expressors (CYP3A5 *1/*1 or *1/*3; TT or CT).
Article: Induction of CYP3A4 by Vinblastine: Role of the Nuclear Receptor NR1I2
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): midazolam
Phenotype category: Other, Metabolism/PK
Significant: no
Association: Allele C is not associated with increased clearance of midazolam in people with Carcinoma, Renal Cell as compared to allele T.
Notes: It's not clear exactly what genotype comparison was done or what the genotypes were, but there was approximately one CT subject and 5 TT subjects.  Frequency entered in Study Parameter section is based on that number.  Subjects were treated with vinblastine/valspodar.   [stat_test: nonparametric 2-sided Wilcoxon signed-rank]
Article: Nicotine Dependence is Associated with Functional Variation in FMO3, an Enzyme that Metabolizes Nicotine in the Brain
Gene: FMO3
Variant/haplotype: rs2266780
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased metabolism of nicotine as compared to genotypes AG + GG.
Notes: Individuals with the AA genotype have a greater percent of both deuterated nicotine and non-deuterated nicotine metabolized to nicotine-N-oxide as compared to the AG or GG genotype.
Article: Influence of ABCC2 and ABCC4 Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients
Gene: ABCC4
Variant/haplotype: rs1751034
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CC + CT is not associated with concentrations of tenofovir in people with HIV Infections as compared to genotype TT.
Article: Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes CT + TT.
Notes: Patients received peginterferon alpha-2A or 2B, along with ribavirin.  This effect was found in HCV genotypes 1 and 4 but not 3.  These patients were coinfected with HIV.  The association was with SVR.  75% of CC vs 38% of CT and TT achieved SVR.  Note: the frequency of CC in patients with spontaneous HCV clearance was significantly higher than in chronically HIV/HCV coinfected patients.
Article: OPRM1, OPRK1 and COMT Genetic Polymorphisms Associated with Opioid Effects on Experimental Pain: A Randomized, Double-Blind, Placebo-Controlled Study
Gene: OPRK1
Variant/haplotype: rs16918875
Drug(s): morphine
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to morphine in healthy individuals as compared to allele G.
Notes: Study-wide significance was set to p<0.017.
Article: An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3′-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with concentrations of efavirenz in people with HIV Infections as compared to genotypes CT + TT.
Notes: Alleles given as A and G.
Article: Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Gene: AMPD1
Variant/haplotype: rs17602729
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G.
Article: Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased response to efavirenz in people with HIV Infections and Tuberculosis as compared to genotypes GG + GT.
Notes: "CYP2B6 516 G>T polymorphism was found to be significantly associated with virological outcomes in patients receiving EFV-based regimen; patients belonging to GG/GT genotype were more likely to have an unfavourable outcome (P=0.022)."
Article: Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): imatinib
Phenotype category: Efficacy
Significant: yes
Association: Genotype GT is associated with increased clinical benefit to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotype GG.
Notes: Alleles complemented. There were no TT homozygotes. "However, a statistically significant difference was noted between the two patient groups regarding the distribution of different genotypes of the ABCG2 C421A polymorphism with predominance of the CA genotype in responder patients (p = 0.0395) (Fig. 2b).; Assessment of molecular response to imatinib based on the BCR-ABL1 transcript level at 12 months. Responders (n = 26); Non-responders (n = 24). "
Article: Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): everolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with concentrations of everolimus in women with Breast Neoplasms as compared to genotype CC.
Notes: Please note: alleles have been complemented to the positive chromosomal strand.
Article: Genetic Variants of SLC22A1 rs628031 and rs622342 and Glycemic Control in T2DM Patients from Northern Mexico
Gene: SLC22A1
Variant/haplotype: rs622342
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AC + CC is associated with increased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to genotype AA.
Notes: "Carriers of at least one minor allele of A-rs628031 and C-rs622342 had lower HbA1c values than individuals homozygous for the major allele in both genes."
Article: An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance
Gene: CYP2C9
Variant/haplotype: rs1799853
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele C is associated with dose of warfarin as compared to allele T.
Notes: This variant annotation is part of a dosing algorithm table based on 8 genetic variants.
Article: CYP2B6 and bupropion’s smoking cessation pharmacology: the role of hydroxybupropion
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*4, CYP2B6*5, CYP2B6*6, CYP2B6*18, CYP2B6*22
Drug(s): bupropion
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *6/*6 + *6/*18 is associated with decreased metabolism of bupropion in people with Tobacco Use Disorder as compared to CYP2B6 *1/*1 + *1/*4 + *1/*5 + *1/*22 + *22/*22.
Notes: Light smokers. Individuals with two copies of a reduced function allele (*6, *18) were grouped into the "slow metabolizer" group. The genotypes within this group were *6/*6 (n=22), *6/*18 (n=8), *6/*6 + *1/*22 (compound heterozygote; n=1). Individuals with *1/*1 (n=48), *1/*4 (n=1), *1/*5 (n=4), *1/*22 (n=4), and *22/*22 (n=1) genotype were considered normal metabolizers. Slow metabolizers had decreased hydroxybupropion levels and hydroxybupropion/bupropion ratios as compared to normal metabolizers. No significant result was seen when considering bupropion levels (p=0.297).
Article: A GENOME-WIDE ASSOCIATION STUDY OF BRONCHODILATOR RESPONSE IN LATINOS IMPLICATES RARE VARIANTS
Gene: IGF2R
Variant/haplotype: rs8191725
Drug(s): salbutamol
Phenotype category: Efficacy
Significant: yes
Association: Genotype AG is associated with increased response to salbutamol in children with Asthma as compared to genotype AA.
Notes: The allele associated with increased response and low frequency is not explicitly stated.  Response is increased for carriers of the rare, minor allele.  This association was significant in the initial GWAS (in GALA II), but it was not significant in an attempted replication by imputation in silico in GALA I.  GALAII genotyping was done using the Affymetrix LAT1 Array, which was designed to capture Latino population variation.
Article: VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide
Gene: VEGFA
Variant/haplotype: rs2010963
Drug(s): cyclophosphamide
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to cyclophosphamide in people with Prostatic Neoplasms as compared to genotypes CG + GG.
Notes: No significant difference genotype frequencies were seen between patients who were responders to chemotherapy, and those who were non-responders. Patients with advanced prostate cancer undergoing metronomic chemotherapy. Responders were classified as patients who had a decrease in prostrate-specific antigen (PSA) of >= 50% and a PSA stabilization of >= 6 months. Patients also received celecoxib and dexamethasone, and some patients received docetaxel-, mitoxantrone-, and vinorelbine-based chemotherapeutic regimens.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: GGCX
Variant/haplotype: rs12714145
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of warfarin in people with heart valve replacement as compared to allele T.
Notes: Samples, genotypes and INRs from a cohort of 551 patients were used to derive an algorithm which was used to predict daily warfarin maintenance dose in a second cohort of 236 patients. Note: the authors state that "SNPs were tested for deviations from HWE using the chi-squared test, and for their association with the warfarin dose by Spearman correlation analysis using a *co-dominant* model."
Article: Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to ethanol as compared to allele A.
Notes: No significant association between this variant and any individual item or total score on the Subjective High Assessment Scale-Expectations (SHAS-E) questionnaire.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: ABCG2
Variant/haplotype: rs4148155
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with decreased response to allopurinol as compared to allele A.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): pantoprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2/*2 is associated with decreased clearance of pantoprazole in healthy individuals as compared to CYP2C19 *1/*1.
Notes: There were 2 *2/*2 and 6 *1/*1.
Article: Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin
Gene: CYP2C9
Variant/haplotype: rs1799853
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin as compared to allele C.
Notes: CYP2C9*2 is associated with a 19% decrement in the warfarin dose per; allele.
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Gene: NELFCD
Variant/haplotype: rs2273359
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: no
Association: Genotype CG is associated with increased response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to genotype CC.
Notes: There is potential for strand confusion with a CG SNP, and it is not clear with respect to the positive chromosomal strand which allele is associated with better response.  The article text states that no GG were observed, but table 2 lists C as the low frequency allele.   The association did not reach genome-wide significance when only PEAR + GERA were analyzed, but this SNP was selected for replication in NORDIL, where the association also did not reach significance.  This association approached genome-wide significance in the meta-analysis of PEAR + GERA + NORDIL.  Observations: 8.21 mm Hg decrease in reduction of systolic blood pressure per C allele in PEAR + GERA, 7.79 mm Hg decrease in reduction in systolic blood pressure per C allele in NORDIL and 8.15 mm Hg decrease in reduction of systolic blood pressure per C allele in PEAR + GERA + NORDIL.
Article: Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin as compared to allele C.
Notes: Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms.
Article: The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients
Gene: FNTB
Variant/haplotype: rs11623866
Drug(s): carboplatin, lonafarnib, paclitaxel
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with response to carboplatin, lonafarnib and paclitaxel in women with Ovarian Neoplasms.
Notes: The authors actually compared progression free survival (PFS) and overall survival (OS) for individuals with the GG, CG, or CC genotypes between treatment arms: lonafarnib, paclitaxel, and carboplatin (LTC) versus paclitaxel and carboplatin (TC) treatment. The PFS and OS were both much lower in women with the GG genotype who were on the LTC treatment arms.
Article: NFAT‐regulated cytokine gene expression during tacrolimus therapy early after renal transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with decreased exposure to tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: Dose normalized tacrolimus exposure was decreased in patients with the CT genotype (CYP3A5 *1/*3) (N=5): at baseline, and at 1.5 hours and 1 week post-dosing as compared with the CC (CYP3A5 *3/*3) genotype (n=23, P=0.033).
Article: Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with increased dose of tacrolimus in children with heart transplantation as compared to CYP3A5 *3/*3.
Notes: Children with the CYP3A5 *1/*1 or *1/*3 genotype required higher doses (mg/kg/12 hours) of tacrolimus as compared to those with the *3/*3 genotype during the first 14 days after transplant.
Article: Effects of SREBF-1a and SCAP polymorphisms on plasma levels of lipids, severity, progression and regression of coronary atherosclerosis and response to therapy with fluvastatin
Gene: SCAP
Variant/haplotype: rs12487736
Drug(s): fluvastatin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fluvastatin in people with Coronary Artery Disease as compared to allele C.
Notes: No association was found with lipid levels, progression or regression with genotypes for this polymorphism. Described as SCAP 2386A/G (I796V) - alleles are complemented here for the plus chromosomal strand.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: IL10
Variant/haplotype: rs1800871
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele G.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.  Authors described association as suggestive in the EA population but it did not survive multiple testing correction. Direction of effect not stated.
Article: A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia
Gene: NUDT15
Variant/haplotype: rs116855232
Drug(s): azathioprine
Phenotype category: Toxicity
Significant: yes
Association: Genotype TT is associated with decreased dose of azathioprine in people with Leukopenia as compared to genotype CC.
Notes: As the number of copies of the T allele increased, the dose of azathioprine at which leukopenia occurred decreased. It was lowest in patients with the TT genotype and showed a gene-dose effect in the order of TT<CT<CC.
Article: Variability in plasma rifampicin concentrations and role of SLCO1B1, ABCB1, AADAC2 and CES2 genotypes in Ethiopian patients with tuberculosis
Gene: ABCB1
Variant/haplotype: rs3842
Drug(s): rifampin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased exposure to rifampin in people with Tuberculosis as compared to genotypes CT + TT.
Notes: "geometric mean of Cmax and AUC0–7h was  significantly higher among patients homozy-gous for  the  variant allele ABCB1c.4036G/G than heterozygous A/G or homozygous wild type (A/A)(Table 3)." Alleles complemented
Article: Targeted Disruption of Organic Cation Transporter 3 Attenuates the Pharmacologic Response to Metformin
Gene: SLC22A3
Variant/haplotype: rs2076828
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to metformin in healthy individuals as compared to allele C.
Notes: A healthy human cohort that was used to determine the effects of functional variants, including rs2076828, on metformin disposition and response. Carriers of the G allele had significantly smaller changes in their glucose AUC (mean ± S.D.; CC, -88 ± 40 mg/dl per hour; CG, -34 ± 51 mg/dl per hour; GG, -41 ± 72 mg/dl per hour) and  significantly lower glucose AUC even before metformin dosing (mean ± S.D.; CC, 376 ± 62 mg/dl per hour; CG, 348 ± 55 mg/dl per hour; GG, 330 ± 41 mg/dl per hour; P < 0.05). Even after adjusting for the differences in glucose AUC before metformin dosing the variant remained significantly associated with metformin response (P < 0.05).
Article: The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): cyclosporine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of cyclosporine in people with Kidney Transplantation as compared to allele T.
Notes: A single steady-state concentration of cyclosporine was collected for each patient 2-7 wks post-transplant and compared to dose of cyclosporine administered to patients at Oslo University Hospital. Reported concentrations are "steady-state dose-adjusted concentration" of cyclosporine. Steady-state is defined as at least 3 days after last dose adjustment for Tac and 4 days for cyclosporine.
Article: Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia
Gene: MTHFR
Variant/haplotype: rs1801131
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes GT + TT.
Notes: Patients with the GG genotype had better overall survival than patients with the GT or TT genotypes. Variant referred to in the paper as A1298C. Please note that alleles have been complemented to the positive strand.
Article: An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele C is associated with dose of warfarin as compared to allele T.
Notes: This variant annotation is part of a dosing algorithm table based on 8 genetic variants.
Article: A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients
Gene: CYP2C18
Variant/haplotype: rs41291550
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased metabolism of warfarin in people with Atrial Fibrillation, venous thromboembolism or Heart Valve Diseases as compared to allele T.
Notes: measured as decreased S-warfarin/R-warfarin ratio and using a genome wide significance threshold of < 3.846 × 10−9. Effect direction from supplementary table S14. Authors note this is "stop gained coding sequence variant of CYP2C18".
Article: Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer
Variant/haplotype: rs6983267
Drug(s): fluorouracil, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fluorouracil, irinotecan and oxaliplatin in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to allele G.
Notes: SNPs were investigated for their effects on response rate, time to progression and overall survival. After accounting for multiple testing there was no association with any SNPs and outcomes of patients with metastatic colorectal cancer.
Article: Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma
Gene: GSK3B
Variant/haplotype: rs3732361
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased concentrations of methotrexate in children with Osteosarcoma as compared to allele G.
Notes: Concentrations refers to area on the concentration at 48 hrs
Article: Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): digoxin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased metabolism of digoxin as compared to genotype GG.
Notes: The finding is that AA is associated with increased plasma levels compared to GG.; [stat_test:mann-whitney u two-sample]