shlokn/autogkb huggingface dataset:
Article: A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics
Gene: CYP4F2
Variant/haplotype: CYP4F2*1, CYP4F2*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP4F2 *3 is associated with increased dose of warfarin as compared to CYP4F2 *1.
Notes: The authors aimed to develop an admixture-adjusted (genetic ancestry) PGx dosing algorithm for warfarin in Caribbean Hispanics from Puerto Rico. [Algorithm R sq.=0.70, MAE = 0.72 mg/day]. When externally validated with 55 individuals from an independent cohort the novel algorithm predicted 58% of the warfarin dose variance [MAE = 0.89 mg/day, 24% mean bias]. Please note: the derivation cohort was 99% male.
Article: Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation
Gene: CFTR
Variant/haplotype: rs75527207
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: not stated
Association: Genotypes AA + AG are associated with response to ivacaftor in people with Cystic Fibrosis.
Notes: Clinical trials were carried out to test efficacy of ivacaftor selecting only patients with the CFTR G551D mutation on at least one allele (genotype AA or AG).
Article: Unidentified CYP2D6 genotype does not affect pharmacological treatment for patients with first episode psychosis
Gene: CYP2D6
Variant/haplotype: CYP2D6 normal metabolizer
Drug(s): clozapine
Phenotype category: Dosage
Significant: yes
Association: CYP2D6 normal metabolizer is associated with increased dose of clozapine in people with Schizophrenia or Psychotic Disorder as compared to CYP2D6 intermediate metabolizer and poor metabolizer.
Notes: "CYP2D6 phenotype was significant for prediction of clozapine, and related to higher dose at NM versus IM, and IM versus PM groups. This model predicted PMs to be administered the lowest chlorpromazine-equivalent dose of clozapine."
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: LRP1
Variant/haplotype: rs4788186
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to platinum in people with Lung Neoplasms as compared to allele G.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.
Article: Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients
Gene: ANGPT1
Variant/haplotype: rs2445365
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bevacizumab in women with Breast Neoplasms as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with concentrations of efavirenz in children with HIV Infections as compared to allele G.
Notes: This is stated in the paper, but supporting data is not shown.; Allele also known as CYP3A4*22.
Article: Impact of the CYP2C8 *3 polymorphism on the drug–drug interaction between gemfibrozil and pioglitazone
Gene: CYP2C8
Variant/haplotype: CYP2C8*1, CYP2C8*3
Drug(s): pioglitazone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C8 *1/*1 is associated with increased concentrations of pioglitazone in healthy individuals as compared to CYP2C8 *1/*3 + *3/*3.
Notes: AUC0-inf and AUC0-48h
Article: Race-specific influence of CYP4F2 on dose and risk of hemorrhage among warfarin users
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with increased dose of warfarin as compared to genotype CC.
Notes: in European americans, but not African americans.
Article: The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients
Gene: PPARA
Variant/haplotype: rs4253728
Drug(s): cyclosporine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with metabolism of cyclosporine in people with Kidney Transplantation as compared to allele G.
Notes: A single steady-state concentration of cyclosporin was collected for each patient 2-7 wks post-transplant and compared to dose of cyclosporin administered to patients at Oslo University Hospital. Reported concentrations are "steady-state dose-adjusted concentration" of cyclosporin.  Steady-state is defined as at least 3 days after last dose adjustment for Tac and 4 days for cyclosporine.
Article: Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies
Gene: CHRNA5
Variant/haplotype: rs67624739
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele del is not associated with response to bupropion, nicotine and varenicline in people with Tobacco Use Disorder as compared to allele CAGAGGGAAATAGGGGCGGGGC.
Notes: Authors looked at the effect of variants on response to the smoking cessation therapies varenicline, bupropion and nicotine replacement therapy. Variant is reported as rs3841324 in the paper and also given the alias rs67624739.
Article: CYP3A4 and CYP3A5 Polymorphisms and Blood Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease
Gene: CYP3A4
Variant/haplotype: rs2246709
Drug(s): amlodipine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are associated with increased response to amlodipine in people with Hypertension as compared to genotype AA.
Notes: People who were carriers for the G allele were more likely to reach the target mean arterial pressure of <= 92 mm Hg when treated with amlodipine compared to AA homozygotes. Please note alleles have been complemented to the plus chromosomal strand.
Article: Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma
Gene: ABCC3
Variant/haplotype: rs4793665
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased concentrations of methotrexate in children with Osteosarcoma as compared to allele T.
Notes: Concentrations refers to area under the concentration time curive (0-48hrs)
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: CYP2D6
Variant/haplotype: rs202102799
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased 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, so assuming minor allele and decreased concentration (beta value in table is negative).
Article: A prospective study of genetic factors, human laboratory phenotypes, and heavy drinking in late adolescence
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Other
Significant: yes
Association: Genotypes AG + GG are associated with increased exposure to ethanol as compared to genotype AA.
Notes: In a session of alcohol self-administration, subjects with the AG or GG genotypes had a greater initial increase in breath alcohol content (BrAC), faster BrAC increases over time and a smaller decline in BrAC at the end of the session. AG or GG subjects also reported engaging in heavy drinking more frequently than AA subjects.
Article: Pharmacometric Characterization of Efavirenz Developmental Pharmacokinetics and Pharmacogenetics in HIV-Infected Children
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype GG is not associated with clearance of efavirenz in children with HIV Infections.
Notes: This SNP did not influence oral clearance or apparent volume of distribution. Variant was described as MDR1-1 C3435T. Please note alleles have been complemented to the plus chromosomal strand.
Article: Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with increased concentrations of tacrolimus in people with Kidney Transplantation as compared to allele G.
Notes: Alleles complemented.
Article: Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): everolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AG + GG are not associated with concentrations of everolimus in women with Breast Neoplasms as compared to genotype AA.
Notes: Please note: alleles have been complemented to the positive chromosomal strand.
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: 24-week, placebo-controlled, double-blind, randomised clinical trial. Patients had the R117H variant and percentage of predicted forced expiratory volume in 1s (% predicted FEV1) of at least 40. Patients received either placebo or ivacaftor 150 mg every 12 hours for 24 weeks (1:1). The treatment difference in mean absolute change in % predicted FEV1 was 2.1 percentage points (p=0.2). But there were significant treatment differences in sweat chloride (-24.0 mmol/L, p<0.0001) and CFQ-R respiratory domain (8.4 points, p=0.009). In subgroup analyses, % predicted FEV1 improved in patients age 18 or older (p=0.01) but not 6-11 years old (favoring placebo, p=0.03). Patients' poly-T status was either 5T or 7T, and significant results for sweat chloride were seen for both types of poly-T status (p<0.0001 and p=0.0003, respectively)
Article: A functional polymorphism in the ABCB1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients
Gene: HTR2A
Variant/haplotype: rs7997012
Drug(s): morphine, nortriptyline
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to morphine and nortriptyline in people with Pain as compared to allele A.
Notes: No significant difference in improvement in pain scores between genotype groups.
Article: Acute administration of ivacaftor to people with cystic fibrosis and a G551D-CFTR mutation reveals smooth muscle abnormalities
Gene: CFTR
Variant/haplotype: rs75527207
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to genotype GG.
Notes: Measured in adult patients, with changes in lung volume, sweat chloride, distensibility, wall thickness, expiratory lumen area, and inspiratory lumen area measured before starting ivacaftor and 48 hour after starting ivacaftor.
Article: PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients
Gene: NR1I3
Variant/haplotype: rs2502815
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with metabolism of efavirenz in people with HIV Infections as compared to genotype GG.
Notes: Plasma levels of efavirenz were not statistically significantly different between the AA, AG, GG genotypes of this SNP.
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: AQP2
Variant/haplotype: rs461872
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to platinum in people with Lung Neoplasms as compared to allele G.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.
Article: Genome-wide association study of patient and clinician rated global impression severity during antipsychotic treatment
Gene: SPOPL
Variant/haplotype: rs10170310
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to olanzapine in people with Schizophrenia as compared to allele A.
Notes: The number of G alleles present in a patient was positively associated with PGI score.
Article: Evaluating metronidazole as a novel, safe CYP2A6 phenotyping probe in healthy adults
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*9, CYP2A6*17
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*2 + *1/*9 + *1/*17 (assigned as reduced metabolizers phenotype) are associated with decreased metabolism of nicotine in healthy individuals as compared to CYP2A6 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: Metabolite ratios for nicotine were significantly reduced in reduced metabolizers compared to normal metabolizers. Subjects were genotyped for the *2, *4, *7, *9, *12, *17, *20, *23-*28, *31 and *35 alleles, although no details of rsIDs are given. No participants were found to have the *7 allele, so no testing for the *8 or *10 alleles was carried out.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with exposure to lopinavir or ritonavir in children with HIV Infections as compared to allele G.
Notes: No association between this variant and AUC0-12 of lopinavir or ritonavir in patients treated with lopinavir/ritonavir. Variant referred to in the paper as C3435T.
Article: Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis
Gene: IL10
Variant/haplotype: rs1800896
Drug(s): etanercept
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to etanercept in people with Arthritis, Rheumatoid as compared to genotypes CT + TT.
Notes: When this genotype is combined with the rs1800629 GG genotype. Those with the CC-GG combination genotype were more likely to be responders to treatment, as compared to those with any other combination of genotypes. However, no significant difference in genotype frequencies was seen between responders and non-responders when considering the rs1800629 or 1800896 SNPs alone. Responders defined using the American College of Rheumatology (ACR) response criteria and response criteria based on the modified disease activity score (DAS)28 index. Non-responders failed to fulfill both these criteria.
Article: Dosing equation for tacrolimus using genetic variants and clinical factors
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: not stated
Association: Allele T is associated with increased dose of tacrolimus in people with Kidney Transplantation as compared to allele C.
Notes: Patients carrying different CYP3A5 genotypes had tacrolimus dose requirement in the order of: CYP3A5*1/*1>CYP3A5*1/*3>CYP3A5*3/*3 at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 week post-transplantation.
Article: Genetic Variation (CHRNA5), Medication (Combination Nicotine Replacement Therapy vs. Varenicline) and Smoking Cessation
Gene: CHRNA3, CHRNA5
Variant/haplotype: rs16969968
Drug(s): varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to varenicline in people with Tobacco Use Disorder as compared to allele A.
Notes: No significant difference in abstinence rates between placebo and varenicline treatment groups.
Article: Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial
Gene: VKORC1
Variant/haplotype: rs7196161
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele A is associated with dose of warfarin in people with Atrial Fibrillation, Pulmonary Embolism, Stroke and Venous Thrombosis as compared to allele G.
Notes: used in a study comparing genotype-guided dosing vs conventional for warfarin initiation. Alleles complemented to plus chromosomal strand. Direction of effect not explicitly stated.
Article: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis
Gene: DOCK6
Variant/haplotype: rs12979813
Drug(s): apremilast
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased clinical benefit to apremilast in people with Psoriasis as compared to allele A.
Notes: "Allele-based association tests detected 64 SNPs displaying nominal p values < 0.05 (Table 2) including 10 SNPs with p values ≤ 0.01. " Table 2 shows frequency of minor allele is responders and non-responders. Responder status maybe defined by PASI score improvement greater than 75% after 24–36 weeks of treatment.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP3A5
Variant/haplotype: rs4646450
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is 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, this was one of the variants that passed validation in both populations. Direction of effect was not stated.
Article: Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): Beta Blocking Agents
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to Beta Blocking Agents in children with Cardiomyopathy, Dilated as compared to allele G.
Notes: Study looked at effect of 'high-risk' genotypes (i.e. genotypes of one or more of rs61767072 del, rs1801253 C or rs1042713 A alleles) on response to beta-blockers. Patients with more 'high-risk' alleles showed a greater response to beta-blockers than those with fewer 'high-risk' alleles.
Article: Screening for UGT1A1 Genotype in Study A5257 Would Have Markedly Reduced Premature Discontinuation of Atazanavir for Hyperbilirubinemia
Gene: UGT1A1
Variant/haplotype: rs887829
Drug(s): atazanavir
Phenotype category: Toxicity
Significant: yes
Association: Genotype TT is associated with increased discontinuation of atazanavir in people with HIV Infections as compared to genotypes CC + CT.
Notes: Atazanavir + ritonavir (atazanavir/r). The TT genotype was associated with a greater cumulative incidence of bilirubin-associated discontinuation of atazanavir in White, Black and Hispanic participants, as well as all participants combined, as compared to the CC or CT genotype. Bilirubin-related events defined as those due to jaundice, elevated bilirubin or hyperpigmentation. Authors suggest that the high rate of discontinuation among White participants in particular may be due to differences in physical manifestations of jaundice.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs111869995
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele A is associated with decreased metabolism of nicotine as compared to allele C.
Notes: Assigned as decreased function following in vitro assessments, in vivo associations and variant construct functional assignments.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs648893
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele A.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: CYP2B6 *6/*6 is associated with decreased dose of methadone in people with Opioid-Related Disorders as compared to CYP2B6 *1/*1.
Notes: This association was not significant. No details about which specific variants/alleles were tested for, however the authors state that genotyping of *1/*6 individuals did not exclude the possibility of them actually being *4/*9.
Article: ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence
Gene: ABCB1
Variant/haplotype: rs2520464
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Genotype TT is not associated with dose of methadone in people with Heroin Dependence as compared to genotypes CC + CT.
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: Impact of Gastric H+/K+-ATPase rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): dexlansoprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2/*2 is associated with decreased metabolism of dexlansoprazole in healthy individuals as compared to CYP2C19 *1/*1.
Notes: CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560) were genotyped but only *2 and *3 were identified. CYP2C19 PMs presented a slower elimination and higher exposure (Cmax and AUCPK) compared to CYP2C19 homEMs, while the elimination and exposure of CYP2C19 hetEMs were intermediate between that of PMs and homEMs. In the 30 mg group, CYP2C19 PMs exhibit significantly higher Cmax, AUCPK, and t1/2 than homEMs and presented remarkably higher AUCPK and t1/2 than those of CYP2C19 hetEMs. CYP2C19 hetEMs shows a significantly higher Cmax and AUCPK compared to CYP2C19 homEMs.