shlokn/autogkb huggingface dataset:
Article: Effect of Genetic Variants on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Involvement of ABCG2, SLCO1B1 and NAT2
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): rosuvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: NAT2 slow acetylator and intermediate acetylator is associated with increased dose-adjusted trough concentrations of rosuvastatin in healthy individuals as compared to NAT2 rapid acetylator.
Notes: "A significant increase in AUC∞/DW (p = 0.004; pmv = 0.001, β = 0.398, R2 = 0.264), AUC72h/DW (p < 0.001; pmv = 0.001, β = 0.427, R2 = 0.302) and Cmax/DW (p < 0.001; pmv < 0.001, β = 0.507, R2 = 0.292) was observed in subjects who were intermediate acetylators (IA) for NAT2, and these parameters were even higher in those who were poor acetylators (PA) compared to rapid acetylators (RA) (Table 3)." Authors reference CPIc and Dutch guidelines but do not specify which variants were measured.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs291028
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele C.
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: The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with trough concentration of lopinavir or ritonavir in men with HIV Infections as compared to allele A.
Notes: No significant association between this variant and trough concentrations of lopinavir or ritonavir in HIV patients treated with lopinavir/ritonavir. Variant referred to in the paper as 388A>G.
Article: Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate
Gene: CYP1A2
Variant/haplotype: CYP1A2 ultrarapid metabolizer
Drug(s): buprenorphine, methadone
Phenotype category: Efficacy
Significant: no
Association: CYP1A2 ultrarapid metabolizer is not associated with response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to CYP1A2 intermediate metabolizer and normal metabolizer.
Notes: Response defined by changes in the rate of dropout from treatment between metabolizer phenotypes. Study genotyped for the CYP1A2 variants -3860G>A (rs2069514), -2467T>delT (rs35694136), -739T>G (rs2069526), -729C>T (rs12720461), -163C>A (rs762551), 125C>G (rs72547511), 558C>A (rs72547513), 2116G>A (rs56276455), 2473G>A (rs72547515), 2499A>T (rs72547516), 3497G>A (assumed that this corresponds to rs55889066), 3533G>A (rs56107638), 5090C>T (rs28399424), 5166G>A (rs72547517) and 5347C>T (rs2470890) and then assigned metabolizer phenotypes.
Article: Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis
Gene: STAT4
Variant/haplotype: rs7574865
Drug(s): etanercept
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to etanercept in people with Arthritis, Rheumatoid as compared to allele G.
Notes: The degree of response was determined by EULAR score.; A significant association between rs7574865 and response to etanercept was seen at two years after beginning treatment. No significant association was seen at six months after beginning treatment.; No significant associations were seen at either time point when response was measured as number of patients in remission or with low disease activity.
Article: A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer
Gene: CYP24A1
Variant/haplotype: rs2762939
Drug(s): calcitriol, cisplatin, docetaxel
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to calcitriol, cisplatin and docetaxel in people with Carcinoma, Non-Small-Cell Lung as compared to allele C.
Notes: No association was seen with overall survival or progression-free survival.
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: APOC3
Variant/haplotype: rs2542052
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AC are not associated with response to fenofibrate in people with Hypertriglyceridemia as compared to genotype CC.
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.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *3/*3 is not associated with concentrations of methadone in people with Opioid-Related Disorders as compared to CYP3A5 *1/*1 + *1/*3.
Notes: No significant difference in concentrations of (R)-, (S)- and (R,S)-methadone between genotypes. No details about which specific variants/alleles were tested for.
Article: Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: XIRP2
Variant/haplotype: rs7606603
Drug(s): atenolol
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to atenolol in people with Hypertension as compared to allele T.
Notes: The C allele was associated with a reduced systolic blood pressure response to atenolol.
Article: Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study
Variant/haplotype: rs77583603
Drug(s): acamprosate
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to acamprosate in people with Alcoholism as compared to allele A.
Notes: The A allele was associated with an increased risk of relapse to drinking in patients undergoing acamprosate treatment.
Article: Influence of ABCB1 gene polymorphisms on the pharmacokinetics of verapamil among healthy Chinese Han ethnic subjects
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): verapamil
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with decreased metabolism of verapamil in healthy individuals as compared to genotypes AA + AG.
Notes: Patients with the GG genotype had lower oral clearance and higher AUC than patients with the AA or AG genotype. This SNP was studied together with rs2032582. Subjects were non-randomly chosen in order to study patients homozygous for the wildtype at both SNPs, heterozygous for both SNPs, and homozygous for the variant at both SNPs.
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: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased clearance of efavirenz in people with HIV Infections as compared to genotype GT.
Notes: As shown by increased plasma concentrations (units = mg/L) for those with the TT genotype compared to those with the GT genotype. Fasting plasma efavirenz concentrations were measured 12 hours after the last dose, and after 12 weeks of treatment.
Article: A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation
Gene: CYP4F2
Variant/haplotype: CYP4F2*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: CYP4F2 *3 is associated with dose of warfarin.
Notes: This study assessed whether a pharmacogenetic algorithm, which included this variant as well as the VKORC1 rs9923231, CYP2C9*2 and CYP2C9*3 variants, is superior in overall anticoagulation control when compared to clinical standard of care.
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: rs8192709
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with clearance of efavirenz in people with HIV Infections as compared to genotypes CT + TT.
Notes: No significant difference in plasma concentrations of efavirenz (units = mg/L) were seen between the three genotypes. Fasting plasma efavirenz concentrations were measured 12 hours after the last dose, and after 12 weeks of treatment. p-value from univariate analysis with plasma concentration as the dependent variable.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: CYP2B6
Variant/haplotype: rs434606
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AG is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype GG.
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: A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*10
Drug(s): hydroxyamitriptyline
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *10/*10 is associated with decreased concentrations of hydroxyamitriptyline in healthy individuals as compared to CYP2D6 *1/*1 + *1/*10.
Notes: as measured by ratio of amitriptyline to hydroxyamitriptyline. Also ratio of nortriptyline to hydroxynortriptyline was significantly lower for *10/*10 compared to *1/*1 or *1/*10.
Article: A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics
Gene: NQO1
Variant/haplotype: rs1800566
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG are associated with increased dose of warfarin as compared to genotype GG.
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: 1) the derivation cohort was 99% male 2) alleles have been complemented to the + chromosomal strand and 3) "variables were included in final lin. reg model if p<0.05 or if association with daily warfarin dose was marginally significant 0.05 = p = 0.20 with strong biological plausability".
Article: β2-Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to atenolol or metoprolol in people with Tachycardia as compared to allele G.
Notes: No significant association between this variant and response to atenolol or metoprolol, as measured by changes in heart rate, in black or Hispanic patients.
Article: Association of CD58 Polymorphism with Multiple Sclerosis and Response to Interferon ß Therapy in A Subset of Iranian Population
Gene: CD58
Variant/haplotype: rs12044852
Drug(s): interferon beta-1a, interferon beta-1b
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to interferon beta-1a and interferon beta-1b in people with Multiple Sclerosis as compared to genotypes AA + AC.
Notes: Patients with relapsing remitting multiple sclerosis. Patients with the CC genotype had a higher increase in mean multiple sclerosis severity score over two years of follow-up, as compared to those with the AA or AC genotype. This SNP was also significantly associated with the occurrence of multiple sclerosis.
Article: PHARMACOGENETIC EFFECTS OF NALTREXONE IN INDIVIDUALS OF EAST ASIAN DESCENT: HUMAN LABORATORY FINDINGS FROM A RANDOMIZED TRIAL
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to naltrexone as compared to allele A.
Notes: No significant medication x genotype interactions on alcohol craving, subjective response to alcohol or alcohol self-administration.
Article: Personalized Tacrolimus Dose Requirement by CYP3A5 but Not ABCB1 or ACE Genotyping in Both Recipient and Donor after Pediatric Liver Transplantation
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: no
Association: Genotype TT is not associated with concentrations of tacrolimus in children with liver transplantation.
Notes: All liver transplant recipients were given tacrolimus 2-3 days post liver transplantation. Weight adjusted dose and concentration to dose ratio (C/D) were the primary outcomes. Dose and C/D were calculated based on measurements taken on day 3, 7 and 14 post-transplantation as well as the the 1st, 3rd, 6th and 12th month post-transplantation. ABCB1 genotype was not significantly associated with C/D of tacrolimus at any time point.
Article: IL28B genotype predicts response to chronic hepatitis C triple therapy with telaprevir or boceprevir in treatment naïve and treatment-experienced patients other than prior partial- and null-responders
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin or telaprevir in people with Hepatitis C as compared to genotypes CT + TT.
Notes: in both naïve patients and treatment-experienced patients.  rs12979860-CC was a stronger predictor of SVR12 than rs8099917-TT.
Article: Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): atazanavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased clearance of atazanavir in healthy individuals as compared to genotypes AG + GG.
Notes: For the haplotype "1236C/2677G/3435C" "subjects with zero CGC copies had faster atazanavir CL/F and lower Cmin compared with individuals with one or two CGC copies"(complemented to plus chromosomal strand). 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 1-7 (atazanavir alone). By the end of day 7 oral clearance of atazanavir was 0.25, 0.18, 0.17 L/h/kg in people with 0, 1 or 2 copies of the haplotype, respectively. Cmin was 66, 159 and 209 ng/mL in people with 0,1 or 2 copies, respectively.
Article: Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite
Gene: CYP2C19
Variant/haplotype: rs12248560
Drug(s): clopidogrel, clopidogrel thiol metabolite H4
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with exposure to clopidogrel or clopidogrel thiol metabolite H4 as compared to allele C.
Notes: Full pharmacokinetic profile was obtained from 17 subjects at  0.5, 1, 2, 3, and 4 h post clopidogrel dose. From 46 subjects samples were collected at 0.5 and 2 h or 1 and 3 h post-dose. Subjects were receiving PCI or elective coronarography.
Article: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): apremilast
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased clinical benefit to apremilast in people with Psoriasis as compared to allele G.
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: ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection
Gene: ITPA
Variant/haplotype: rs1127354
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes AA + AC.
Notes: The authors actually compared platelet counts between patients with normal or deficient ITPase activity. Patients with the composite genotypes of rs1127354 CC and rs7270101 AA had "normal ITPase activity" and all other genotype combinations were classified as "deficient". Univariable logistic regression normal ITPase activity was not significantly associated with virological relapse.
Article: Effects of genetic variants of organic cation transporters on metformin response in newly diagnosed patients with type 2 diabetes
Gene: ATM
Variant/haplotype: rs1800058
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with decreased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
Notes: "Other SNPs (rs4621031, rs34399035, rs1800058, and rs11212617) had no significant impact on metformin response. " This was not polymorphic (all CC) in this population
Article: The Effect of Gene Variants on Levonorgestrel Pharmacokinetics when Combined with Antiretroviral Therapy containing Efavirenz or Nevirapine
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): levonorgestrel
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT are associated with decreased concentrations of levonorgestrel in women with HIV Infections as compared to genotype GG.
Notes: in patients treated with levonorgestrel implant plus efavirenz. The authors hypothesize that the high EFV plasma concentrations associated with these SNPs may result in greater EFV induction of CYP3A4, resulting in increased LNG metabolism and lower LNG exposure in the patients who were heterozygous or homozygous for CYP2B6 516G>T or CYP2B6 15582C>T.
Article: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): selumetinib
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of selumetinib in healthy individuals as compared to allele A.
Notes: Not associated with AUC, AUC0-12 when allele was assessed within ethnic groups (Asian, White, Black) and when all ethnic groups were pooled together. Only P-values for AUC presented here.
Article: Genome‐Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β‐Blockers
Gene: SNX9
Variant/haplotype: rs2364349
Drug(s): atenolol, metoprolol
Phenotype category: PD
Significant: yes
Association: Allele A is associated with decreased response to atenolol or metoprolol in people with Hypertension as compared to allele G.
Notes: as measured by decreased heart rate.
Article: A Phase I, Open-Label, Fixed Sequence Study to Investigate the Effect of Cytochrome P450 2D6 Inhibition on the Pharmacokinetics of Ulotaront in Healthy Subjects
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer
Drug(s): ulotaront
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 poor metabolizer is associated with decreased clearance of ulotaront in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: "This genotyping assay solely detects variants; *1(WT),*2, *3, *4, *5, *7, *8, *9, *10, *11, *15, *17, *29,; *35, and *41. Defnitions of normal metabolizer (NM),; intermediate metabolizer, and PM follow Clinical Pharmacogenetics Implementation Consortium" "mean; CL/F from PMs was generally lower in comparison with; the mean CL/F from non-PMs " "As expected,; CYP2D6 inhibition by paroxetine decreased ulotaront CL/F; to a level approximating ulotaront CL/F in CYP2D6 PMs" "Strong CYP2D6 inhibitors are reported; to pheno-covert CYP2D6 NMs into PMs"
Article: ABCB1, CYP2B6, and CYP3A4 Genetic Polymorphisms do not Affect Methadone Maintenance Treatment in HCV-positive Patients
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of methadone in men with Heroin Dependence as compared to allele G.
Article: Pharmacogenetics of Asthma Controller Treatment
Gene: CHRM2
Variant/haplotype: rs8191992
Drug(s): fluticasone/salmeterol
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with response to fluticasone/salmeterol in people with Asthma as compared to allele T.
Notes: The "major" allele is associated with increased response.  It is not clear whether that is A or T on the positive chromosomal strand.
Article: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
Notes: Please note: alleles have been complemented to the + chromosomal strand.
Article: Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics
Gene: ABCC2
Variant/haplotype: rs2273697
Drug(s): ezetimibe
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is associated with increased dose-adjusted trough concentrations of ezetimibe in healthy individuals as compared to genotypes AG + GG.
Notes: "Volunteers with the ABCC2 rs2273697 A/A genotype showed a; trend to higher Cmax/DW compared to the G/A genotype (puv =; 0.087, pmv = 0.048, β = 0.267, R2 = 0.067) (Table 4)."
Article: Contribution of BDNF and DRD2 genetic polymorphisms to continued opioid use in patients receiving methadone treatment for opioid use disorder: an observational study
Gene: DRD2
Variant/haplotype: rs1799978
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele T.
Notes: Response to methadone was measured as the number of urine screens which were positive for opioids during methadone treatment.; No participants were found to have the CC genotype.; Please note that alleles have been complemented to the positive strand.