shlokn/autogkb huggingface dataset:
Article: CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis
Gene: STAT6
Variant/haplotype: rs1059513
Drug(s): esomeprazole
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT are associated with increased response to esomeprazole in children with eosinophilic esophagitis as compared to genotype TT.
Notes: NOTE: Alleles are not provided in article. For PPI-REE outcome (dominant genetic model, covariates as above), individuals who carried 1 or 2 copies of rs1059513 had 6.2-fold better odds of achieving a PPI responsive esophageal eosinophilia (PPI-REE)  outcome after PPI therapy than individuals who did not carry rs1059513 (PPI-REE OR [95% CI] = 6.16 [1.44, 26.35], P = 0.028)
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRK1
Variant/haplotype: rs997917
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele T.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy. Please note that alleles have been complemented to the positive strand.
Article: Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): lansoprazole, omeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *1/*1 is not associated with response to lansoprazole or omeprazole in healthy individuals as compared to CYP2C19 *1/*2.
Notes: No significant difference in the mean percentage of time with intragastric pH greater than 4.0 was seen between the genotypes in subjects taking omeprazole (10 mg/day) or lansoprazole (15 mg/day). Subjects were treated with either drug for 6 days, in a crossover fashion; mean percentage of time with intragastric pH greater than 4.0 was measured on day 1 and day 6 after initiation of treatment.
Article: Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Variant/haplotype: rs2650972
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: Warfarin Dosage Response Related Pharmacogenetics in Chinese Population
Gene: GGCX
Variant/haplotype: rs699664
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Genotypes CT + TT are not associated with concentrations of warfarin in people with heart valve replacement as compared to genotype CC.
Notes: 130 plasma samples were obtained 12 hours after the last dose of warfarin. The plasma warfarin concentrations of these samples were comparing plasma concentration within the group of patients with INR between 1.5–2.5 (n = 92) between genotype groups.
Article: Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9 intermediate metabolizer
Drug(s): phenytoin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 intermediate metabolizer is associated with increased concentrations of phenytoin as compared to CYP2C9 normal metabolizer.
Notes: "Sufficient data were available to meaningfully quantify the difference in phenytoin plasma concentrations between the different CYP2C9 and CYP2C19 metabolizer phenotypes. The CYP2C9 intermediate metabolizers had 46% (95% CI, 33%-61%) higher phenytoin plasma concentrations compared with the CYP2C9 normal metabolizers (Figure 2 and Table 3). Insufficient data were available for a meaningful analysis of the association between the very rare CYP2C9 poor metabolizers phenotype and differences in phenytoin plasma concentrations. However, the only study suitable for inclusion, which included 5 CYP2C9 poor metabolizers and 41 CYP2C9 normal metabolizers, showed a very profound increase in phenytoin plasma concentration of 134% in poor metabolizers compared with normal metabolizers." "Decreased activity: CYP2C9*2: rs1799853; Abolished activity: CYP2C9*3: rs1057910"
Article: IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti–IL-4 receptor α antagonist
Gene: IL4R
Variant/haplotype: rs3024530
Drug(s): pitrakinra
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to pitrakinra in people with Asthma as compared to genotypes AG + GG.
Notes: Subjects with the AA genotype have a reduced frequency of asthma exacerbations compared to those with the AG + GG genotypes.
Article: Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *2 + *3 are associated with decreased dose of warfarin in people with venous thromboembolism as compared to CYP2C9 *1/*1.
Notes: CYP2C9 and VKORC1 variants are analyzed together to divide patients into three warfarin sensitivity types (normal, sensitive and highly sensitive). "Warfarin sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time over-anticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252)."
Article: Variation in P450 oxidoreductase (POR) A503V and flavin containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism but does not alter cigarette consumption
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12, CYP2A6*17, CYP2A6*20, CYP2A6*23, CYP2A6*24, CYP2A6*25, CYP2A6*26, CYP2A6*27, CYP2A6*28, CYP2A6*35
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *2 + *4 + *9 + *17 + *20 + *23 + *25 + *26 + *27 + *28 + *35 + *12 + *24 (assigned as low activity phenotype) is associated with decreased metabolism of nicotine as compared to CYP2A6 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: CYP2A6 reduced metabolizers(participants with 1 or more of the alleles: *2,*4,*9,*17,*20,*23,*25-*28,*35,*12,*24) showed 50% higher nicotine AUC and 40% lower 3HC/COT in non-smokers.
Article: Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction
Gene: NTRK2
Variant/haplotype: rs1948308
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Genotype GG is associated with decreased dose of methadone in people with Heroin Dependence as compared to genotypes AA + AG.
Notes: This association was statistically significant after permutation analysis based on 40,000 replicates, but not statistically significant after adjusting for testing for multiple SNPs (Bonferroni correction). Note; this SNP was in LD with rs4358872, rs2378676, and rs4877900 (r^2>0.7).
Article: Toll-Like Receptor 4 Polymorphism Associated with the Response to Whole-Cell Pertussis Vaccination in Children from the KOALA Study
Gene: TLR4
Variant/haplotype: rs2770150
Drug(s): Pertussis vaccines
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to Pertussis vaccines in children as compared to genotype AG.
Notes: Patients with the GG genotype had a lower pertussis toxin-specific immunoglobulin G (PT-IgG) titer following whole-cell pertussis vaccination as compared to those with the AG genotype. The IgG antibody titer against PT correlates with protection against disease. Please note alleles have been complemented to the plus chromosomal strand.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs2043144
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele T.
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: Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine
Gene: TPMT
Variant/haplotype: TPMT*1, TPMT*3A, TPMT*3C
Drug(s): azathioprine
Phenotype category: Dosage, Efficacy, Toxicity
Significant: not stated
Association: TPMT *3A/*3C is associated with decreased dose of azathioprine in people with Crohn Disease as compared to TPMT *1/*1.
Notes: Toxicity could be avoided and treatment was still effective if the azathioprine dose was dramatically lowered.
Article: Pharmacogenetic Pathway Analysis of Docetaxel Elimination
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): docetaxel
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with increased clearance of docetaxel in people with Neoplasms as compared to allele T.
Notes: The C allele corresponds with CYP3A*1B. The presence of the CYP3A4*1B and was associated with a 62% (P=0.055) increase in docetaxel clearance.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DDC
Variant/haplotype: rs11575553
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of methadone in people with Heroin Dependence as compared to allele G.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele A.
Notes: No significant difference in methadone dose between genotypes. No details about which specific variants/alleles were tested for. Variant referred to as C3435T. Please note that alleles have been complemented to the positive strand.
Article: Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention
Gene: ABCC2
Variant/haplotype: rs2273697
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with decreased response to clopidogrel in people with Coronary Artery Disease as compared to genotypes AG + GG.
Notes: "neither ABCC2 rs2273697 nor ABCC2 rs3740066 polymorphisms affected PAIR% values "
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: rs10048158
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: no
Association: Allele C 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 T.
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: Poor Warfarin Dose Prediction with Pharmacogenetic Algorithms that Exclude Genotypes Important for African Americans
Variant/haplotype: rs12777823
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG is associated with decreased dose of warfarin as compared to genotype GG.
Notes: Observed dose (mg/kg): GG (n=157) 8 (5.0–8.6), GA (n=97) 5.7 (4.3–7.5), AA (n=20) 5.2 (4.3–7.3) p=0.0047
Article: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs1707
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotypes CT + TT.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). Neither were significantly associated with any genotype.
Article: Genetic variants in the KIF6 region and coronary event reduction from statin therapy
Gene: KIF6
Variant/haplotype: rs9462535
Drug(s): atorvastatin, pravastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AC are associated with increased response to atorvastatin or pravastatin.
Article: TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy
Variant/haplotype: rs10499194
Drug(s): Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with decreased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to allele C.
Notes: using either the absolute change in DAS28 or the proportion of good responders and non-responders as outcomes.
Article: Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype GG is not associated with dose-adjusted trough concentrations of tacrolimus in people with Arthritis, Rheumatoid or Lupus Erythematosus, Systemic as compared to genotypes AA + AG.
Notes: No significant difference in the dose-adjusted concentration of tacrolimus was seen between the genotypes. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities
Gene: CYP2B6
Variant/haplotype: rs2279344
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with concentrations of methadone as compared to allele G.
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: Efficacy
Significant: no
Association: CYP2C9 *1/*3 + *2/*2 + *2/*3 + *3/*3 are not associated with response to methadone in people with Opioid-Related Disorders as compared to CYP2C9 *1/*1 + *1/*2.
Notes: No significant difference in genotype or phenotype frequencies between responders and non-responders, as defined by drug misuse during methadone maintenance therapy. No details about which specific variants/alleles were tested for.
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: UGT1A4
Variant/haplotype: rs2011404
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with increased concentrations of clozapine in people with Schizophrenia or Psychotic Disorder as compared to allele T.
Notes: "In the model adjusted for clinical predictors of clozapine concentration, including smoking status and cumulative dose of clozapine, five SNPs (rs28371726 and rs202102799 in CYP2D6; rs4148323 and rs34946978 in UGT1A1; and rs2011404 in UGT1A4) showed significant associations with clozapine concentration. The rs number for each SNP associated with clozapine concentration is shown in Table 3." Table does not state which allele or direction of effect for these SNPs, but lists as c.471T > C so assuming C as effect allele and increased concentration (beta value in table is positive).
Article: Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *2 + *3 are associated with dose of warfarin in children as compared to CYP2C9 *1.
Notes: In univariate analysis the weekly warfarin dose was most strongly associated with age, weight, height, BSA, sex, and VKORC1 genotype. There was a trend of association between the presence of 1 or 2 CYP2C9 variant alleles and decreased dose requirement but the association was not significant (this is the first reported p-value).; After statistical adjustment for confounding variables the multivariate analysis showed that CYP2C9 genotype (number of variant * alleles, 0,1,2) explained 2% of the observed inter individual variability in warfarin dose (this is the second reported p-value).
Article: Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): ritonavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased clearance of ritonavir in healthy individuals as compared to genotypes AC + CC.
Notes: For the haplotype "1236C/2677G/3435C" "overall ritonavir CL/F was ∼1.9-fold faster in subjects with zero versus two CGC haplotype""and was 1.47-fold faster in subjects with zero versus one CGC copy". In this two-phase study, healthy participants were given atazanavir only for 7 days and then were co-administered ritonavir as a booster for days 8-14. The results here are for day 8-14 (atazanavir plus ritonavir).
Article: Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance and metabolism
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*4, CYP2B6*6
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *1/*4 + *4/*6 is associated with increased clearance of methadone in healthy individuals as compared to CYP2B6 *1/*1.
Notes: PK measures were AUC, clearance, peak concentration, exposure.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele T.
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, this was one of the variants that passed validation in both populations. Direction of effect was not stated.
Article: A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients
Gene: CYP2C9
Variant/haplotype: rs9332241
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased metabolism of warfarin in people with Atrial Fibrillation, venous thromboembolism or Heart Valve Diseases as compared to allele C.
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 "three prime untranslated region variant of CYP2C9, in LD with CYP2C9*8".
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs2112865
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to olanzapine in people with Schizophrenia as compared to genotypes AG + GG.
Notes: Not significant after correction for multiple testing using the False Discovery Rate. Response was assessed by change in the total Positive and Negative Syndrome Scale (PANSS) score.
Article: PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients
Gene: NR1I3
Variant/haplotype: rs2307424
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype GG is not associated with metabolism of efavirenz in people with HIV Infections as compared to genotype AG.
Notes: Plasma levels of efavirenz were not statistically significantly different between the GG and AG genotypes of this SNP. Alleles have been complemented to the plus chromosomal strand.
Article: ABC Transporter Polymorphisms are Associated with Irinotecan Pharmacokinetics and Neutropenia
Gene: ABCC1
Variant/haplotype: rs3743527
Drug(s): SN-38
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with exposure to SN-38 in people with Colorectal Neoplasms as compared to genotype CC.
Notes: AUC of SN-38 was adjusted for irinotecan dose.
Article: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain
Gene: COMT
Variant/haplotype: rs4680
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.
Notes: This was for alleviation of pain from cancer.  The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs2239393, rs4818, rs740603, rs174699, rs165728).  The haplotype was associated with a dose reduction factor of 0.71 .  Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value.  Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.
Article: The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects
Gene: CYP2C8
Variant/haplotype: CYP2C8*1, CYP2C8*3
Drug(s): ibuprofen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C8 *3 is associated with decreased metabolism of ibuprofen in healthy individuals as compared to CYP2C8 *1/*1.
Notes: The effect on (R)-ibuprofen pharmacokinetics is associated with the CYP2C8*3 allele. There was a statistically significant gene–dose effect for AUC (P = 0.025), t1/2 (P < 0.025) and drug clearance (P = 0.030). Most individuals that possessed the CYP2C8*3 allele were also carriers of CYP2C9*2. However, there were no significant differences between the carriers of CYP2C8*3 who did or did not possess the CYP2C9*2 allele.
Article: Reduced Renal Clearance of Cefotaxime in Asians with a Low-Frequency Polymorphism of OAT3 (SLC22A8)
Gene: SLC22A8
Variant/haplotype: rs11568482
Drug(s): cefotaxime
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AT is associated with decreased clearance of cefotaxime in healthy individuals as compared to genotype TT.