shlokn/autogkb huggingface dataset:
Article: Blood pressure signature genes and blood pressure response to thiazide diuretics: results from the PEAR and PEAR-2 studies
Variant/haplotype: rs11065987
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with increased response to hydrochlorothiazide in people with Hypertension as compared to genotype GG.
Notes: rs11065987 was selected as a representative SNP of rs11065987, rs653178, rs10774625 and rs11066301, all of which are in high linkage disequilibrium with each other. The A allele of rs11065987 was associated with a greater decrease in both systolic and diastolic blood pressure following treatment with hydrochlorothiazideas compared to the GG genotype.
Article: Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizer
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 poor metabolizer is associated with increased clinical benefit to antidepressants in people with Depressive Disorder, Major as compared to CYP2C19 normal metabolizer.
Notes: "Overall, PMs in CYP2C19 showed a higher remission rate with nominal significance (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, Fig. ​Fig.2a)2a) but did not meet correction for multiple testing. The percentage improvement analysis showed a non-significant higher efficacy in PMs (SMD = 0.13, 95% CI [−0.03, 0.29], p = 0.101)."
Article: Pharmacogenetic association of the APOA1/C3/A4/A5 gene cluster and lipid responses to fenofibrate: the Genetics of Lipid-Lowering Drugs and Diet Network study
Gene: APOA4
Variant/haplotype: rs5104
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CT are not associated with response to fenofibrate in people with Hypertriglyceridemia as compared to genotype TT.
Notes: No significant difference in the change in plasma triglyceride (TG) or high-density lipoprotein (HDL) levels between genotypes was seen, after three weeks of treatment with fenofibrate. Please note alleles have been complemented to the plus chromosomal strand.
Article: Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study
Variant/haplotype: rs12944940
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with increased response to boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin or telaprevir in people with Hepatitis C, Chronic as compared to allele C.
Notes: This variant was not significantly associated with SVR to triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.
Article: The use of ivacaftor in CFTR mutations resulting in residual functioning protein
Gene: CFTR
Variant/haplotype: rs121909011
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to allele T.
Notes: Investigation of ivacaftor treatment in patients with CFTR variants conferring residual CFTR function, comparing patients with ivacaftor treatment to those without. Genotypes of the patients receiving ivacaftor were R347P/L1065P, 2789+5G/R1066C, S912X/D579G, S912X/D579G, del F508/R352Q, G542X/D1152H, and W1282W/D1152H. The outcomes measured were FEV1 %predicted, increase in BMI, CFQ-R, and number of exacerbations.
Article: Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is associated with decreased dose of warfarin.
Article: Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients
Gene: SLC19A1
Variant/haplotype: rs1051266
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C.
Article: Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease
Gene: ITGB3
Variant/haplotype: rs58847127
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with increased resistance to clopidogrel in people with Coronary Disease as compared to allele G.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Gene: CYP1A2
Variant/haplotype: rs4646425
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele T.
Article: Genetic Association of Olanzapine Treatment Response in Han Chinese Schizophrenia Patients
Variant/haplotype: rs12610827
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased clinical benefit to olanzapine in people with Schizophrenia as compared to allele G.
Notes: Authors state "In this study, Han Chinese SCZ patients who carried allele T in SNP rs12610827 showed more good response in OLA treatment."
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: NR1I2
Variant/haplotype: rs1054190
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.
Article: Impact of Pharmacogenetic Markers of CYP2B6, Clinical Factors, and Drug-Drug Interaction on Efavirenz Concentrations in HIV/Tuberculosis-Coinfected Patients
Gene: CYP2B6
Variant/haplotype: rs2279343
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with decreased clearance of efavirenz in people with HIV Infections as compared to genotype AA.
Notes: As shown by increased plasma concentrations (units = mg/L) for those with the AG genotype compared to those with the AA genotype. Fasting plasma efavirenz concentrations were measured 12 hours after the last dose, and after 12 weeks of treatment.
Article: Efficacy and safety of ivacaftor treatment: randomized trial in subjects with cystic fibrosis who have an R117H-CFTR mutation
Gene: CFTR
Variant/haplotype: rs78655421
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with response to ivacaftor in people with Cystic Fibrosis.
Notes: Extension study of KONDUCT. Patients underwent a washout period then an interim analysis at 12 weeks. Placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement (absolute change from post-washout baseline at week 12: placebo-to-ivacaftor 5.0 percentage points (p=0.0005), ivacaftor-to-ivacaftor 6.0 percentage points (p=0.006)). There was also improvement in CFQ-R respiratory domain.
Article: Genetic Determinants of Response to Warfarin during Initial Anticoagulation
Gene: VKORC1
Variant/haplotype: rs2884737
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with decreased dose of warfarin as compared to genotype AA.
Notes: With *1/*2 (AC) requiring intermediate dose. This was most marked at day 28 to end of follow-up with average doses of 3.66mg/day for *2*2 (HaplotypeA/HaplotypeA"), 4.45mg/day for HaplotypeA/nonA and 5.68mg/day for nonA/nonA. Authors also used rs9923231, rs9934438, rs8050894, and rs2359612 to define HaplotypeA.
Article: OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): morphine
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of morphine in people with Neoplasms as compared to allele G.
Notes: The setting was for palliative care of cancer patients.
Article: Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): tenofovir alafenamide
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with decreased concentrations of tenofovir alafenamide in healthy individuals as compared to genotype GG.
Notes: "Through linear regression analysis CYP3A4*22 522-191C>T (rs35599367) was significantly associated with log10 tenofovir alafenamide plasma AUC at visit day 56 (P = 0.033, β = 0.25), with a 39% difference in tenofovir alafenamide AUC between homozygous CC (n = 17) and heterozygous CT (n = 4) individuals. Within our population no subjects possessed the homozygous variant genotype for CYP3A4*22 522-191C>T." Alleles complemented to plus chromosomal strand.
Article: ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Genotype AA is not associated with dose of methadone in people with Heroin Dependence as compared to genotypes AG + GG.
Notes: Please note that alleles have been complemented to the positive strand. Genotypes were not associated with the need for a higher (>150mg) or lower (<150 mg) dose of methadone.
Article: Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizer and intermediate metabolizer genotypes
Drug(s): esomeprazole, pantoprazole, rabeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 intermediate metabolizer and poor metabolizer is not associated with increased clinical benefit to esomeprazole, pantoprazole or rabeprazole in people with Helicobacter Infections as compared to CYP2C19 normal metabolizer.
Notes: in meta-analysis of cure rates of H. pylori in triple therapy.
Article: Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study
Gene: APOH
Variant/haplotype: rs52797880
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with increased response to boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin or telaprevir in people with Hepatitis C, Chronic as compared to allele G.
Notes: This variant was not significantly associated with SVR to triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.
Article: Oxidative Stress-Related Genetic Polymorphisms Are Associated with the Prognosis of Metastatic Gastric Cancer Patients Treated with Epirubicin, Oxaliplatin and 5-Fluorouracil Combination Chemotherapy
Gene: NOS3
Variant/haplotype: rs1799983
Drug(s): epirubicin, fluorouracil, oxaliplatin
Phenotype category: Efficacy
Significant: not stated
Association: Allele G is not associated with response to epirubicin, fluorouracil and oxaliplatin in people with Neoplasm Metastasis and Stomach Neoplasms.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: CYP2C19
Variant/haplotype: rs3758580
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype CC.
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: Pharmacogenetics of plasma dolutegravir exposure during 1-month rifapentine/isoniazid treatment of latent tuberculosis
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): dolutegravir
Phenotype category: Metabolism/PK
Significant: no
Association: NAT2 slow acetylator is not associated with increased dose-adjusted trough concentrations of dolutegravir in people with HIV infectious disease and Tuberculosis as compared to NAT2 rapid acetylator.
Notes: "no association between NAT2 acetylator; status and dolutegravir Ctrough"
Article: Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*3
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *1/*3 + *3/*3 are not associated with resistance to clopidogrel in people with Stroke as compared to CYP2C19 *1/*1.
Article: CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor and ultrarapid metabolizers
Drug(s): opioids
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 poor and ultrarapid metabolizers are associated with decreased response to opioids in people with Pain as compared to CYP2D6 intermediate metabolizer and normal metabolizer.
Notes: After adjusting for age and gender, subjects with poor or ultrarapid metabolizer phenotype are 2.6 times more likely to experience poor pain control.
Article: Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African-Americans with opioid use disorder
Gene: OPRD1
Variant/haplotype: rs678849
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to methadone in people with Opioid-Related Disorders as compared to genotypes CT + TT.
Notes: Efficacy was determined by the number of opioid-positive urine screens recorded during treatment.
Article: Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): nevirapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased metabolism of nevirapine in people with HIV Infections as compared to genotypes GG + GT.
Article: Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort
Gene: NR1I2
Variant/haplotype: rs2472682
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of warfarin as compared to allele A.
Notes: Warfarin dose requirement was defined as the reported daily dose at 3 months following treatment initiation.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs2456568
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 G.
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: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: CLCN6, MTHFR
Variant/haplotype: rs1801133
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of tenofovir in people with HIV Infections as compared to allele G.
Notes: Significance threshold was set at 4.5E-3.
Article: Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance
Gene: POR
Variant/haplotype: rs1057868
Drug(s): donepezil
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with clearance of donepezil in people with Alzheimer Disease as compared to genotype CC.
Notes: Genotypes of TT, CT and CC did not influence donepezil clearance in a covariate model. Alleles have been complemented to the plus chromosomal strand.
Article: Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment
Gene: OPRM1
Variant/haplotype: rs2236259
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methadone in people with Heroin Dependence as compared to allele T.
Notes: This SNP was not significantly associated with compliance with methadone maintenance therapy or 'negative rate of morphine urine test'.
Article: Association of Genetic Variants With Response to Anti–Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration
Gene: INHBA
Variant/haplotype: rs2237435
Drug(s): bevacizumab, ranibizumab
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bevacizumab and ranibizumab in people with as compared to allele C.
Notes: The authors performed GWAS in a discovery cohort, and did a replication analysis.
Article: Impact of CYP3A4*22 on Pazopanib Pharmacokinetics in Cancer Patients
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): pazopanib
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with decreased clearance of pazopanib in people with Neoplasms as compared to genotype GG.
Notes: There were homozygous AA in the cohort. Alleles complemented to plus chromosomal strand. Variant described as CYP3A4 rs35599367 15389C>T *22
Article: Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives – Results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: HFE
Variant/haplotype: rs1799945
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to atenolol in people with Hypertension as compared to allele C.
Notes: Not significant when using Bonferroni-corrected alpha of 0.0014. Response was assessed by change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 9 weeks of treatment.
Article: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A4
Variant/haplotype: rs4986910
Drug(s): ambrisentan, aripiprazole, atorvastatin, donepezil, olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of ambrisentan, aripiprazole, atorvastatin, donepezil or olanzapine in healthy individuals as compared to allele A.
Notes: No significant changes in PK parameters in the presence of the G allele. The G allele is also referred to in the paper as the CYP3A4*3 allele.
Article: CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased concentrations of atorvastatin in people with Cardiovascular Disease or Hyperlipidemias as compared to genotype CT.
Notes: "Patients with the C/C genotype had higher plasma atorvastatin levels (8.07 ± 2.33) than did those with the T/C genotype (3.30 ± 1.00) (P value < 0.001) (Table 5).; Pearson’s analysis revealed statistically significant correlations (P values < 0.001) between atorvastatin plasma levels (in ng/ml) and both genotypes of CYP3A5*3 (T/C) and (C/C). There was a strong indirect relationship between the T/C genotype and disease severity (r = − 0.73, n = 32). For the (C/C) genotype, there was a strong and direct relationship (r = 0.80, n = 67) (Table 3)." No TT were reported.
Article: Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking
Gene: CHRNA3
Variant/haplotype: rs578776
Drug(s): nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to nicotine or varenicline in people with Tobacco Use Disorder as compared to genotypes AA + AG.
Notes: Response here refers to smoking cessation outcomes at 7 days and nicotine refers to nicotine patches. Smoking cessation outcomes at 6 months and 12 months were also not significantly associated with genotype.
Article: Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*9, CYP2A6*10
Drug(s): 3-hydroxycotinine, 3-hydroxycotinine glucuronide
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1 + *2 (assigned as normal metabolizer and intermediate metabolizer phenotype) is associated with increased concentrations of 3-hydroxycotinine and 3-hydroxycotinine glucuronide in people with Tobacco Use Disorder as compared to CYP2A6 *10 + *9 (assigned as poor metabolizer phenotype) .
Notes: Authors compared NMR nicotine metabolic ratio using 3-hydroxycotinine to cotinine in plasma and 3-hydroxycotinine and 3-hydroxycotinine glucuronide to cotinine in urine. Alleles measured were *1X2A, *1B, *2, *4, *9, *7, *8, *10 (composed of *7 and *8), *12, and *35. Activity scores were assigned by diplotype.
Article: The largest prospective warfarin-treated cohort supports genetic forecasting
Gene: CYP2C9
Variant/haplotype: CYP2C9*2
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *2 is associated with decreased dose of warfarin.
Notes: CYP2C9*2 and *3 explained 12% (P = 6.63 x 10(-34)) of the variation in warfarin dose.
Article: Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2B6 *6 is associated with increased concentrations of efavirenz in people with HIV as compared to CYP2B6 *1/*1.
Article: Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study
Gene: GLA
Variant/haplotype: rs397515870
Drug(s): migalastat
Phenotype category: Efficacy
Significant: not stated
Association: Allele G is associated with increased response to migalastat in people with Fabry Disease.
Notes: Patients carrying the G allele showed improvements in renal function, cardiac geometry (specifically, reductions in left ventricular mass index) and gastrointestinal symptoms as well as reductions in GL-3 inclusions and plasma lyso-Gb3 and an increase in PBMC alpha-Gal A activity when treated with migalastat. Clinical benefit of migalastat was not substantially affected by disease severity. This variant was designated as an 'amenable variant' to migalastat treatment following an in vitro assay where migalastat increased the activity of alpha-Gal A by at least 3%. As all data were derived from post hoc analysis, statistical analyses were not carried out. Variant referred to as Pro205Thr in the paper.