shlokn/autogkb huggingface dataset:
Article: Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Gene: CYP3A5
Variant/haplotype: rs10264272
Drug(s): lumefantrine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased concentrations of lumefantrine in women with Malaria and Pregnancy as compared to allele C.
Notes: Median concentrations of lumefantrine 7 days after beginning treatment with artemether-lumefantrine was significantly higher in carriers of the T allele as compared to non-carriers.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs2829163
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with clearance of tenofovir in people with HIV Infections as compared to allele C.
Notes: Significance threshold was set at 5E-9. This variant was in linkage disequilibrium with rs7282679.
Article: Estimating the In Vivo Function of CYP2D6 Alleles through Population Pharmacokinetic Modeling of Brexpiprazole
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*9, CYP2D6*10, CYP2D6*14, CYP2D6*17, CYP2D6*29, CYP2D6*41
Drug(s): brexpiprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *9 +*10 + *14 + *17 + *29 + *41 is associated with decreased metabolism of brexpiprazole as compared to CYP2D6 *1.
Notes: in patients and healthy individuals from clinical studies.  "Among the decreased function alleles, the following; enzyme activities relative to CYP2D6*1 were estimated: 23% for CYP2D6*9 (n = 20), 32% for CYP2D6*10 (n = 62),; 64% for CYP2D6*14 (n = 1), 4% for CYP2D6*17 (n = 37), 4% for CYP2D6*29 (n = 13), and 9% for CYP2D6*41 (n = 64). "
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: GREM2
Variant/haplotype: rs10802887
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to allopurinol as compared to allele A.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: Modelling the influence of MDR1 polymorphism on digoxin pharmacokinetic parameters
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): digoxin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of digoxin in healthy individuals as compared to genotypes AG + GG.
Notes: AA homozygotes had a lower apparent volume of distribution compared to carriers of the G allele. Please note alleles have been complemented to the plus chromosomal strand.
Article: Replicated Association between an IL28B Gene Variant and a Sustained Response to Pegylated Interferon and Ribavirin
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b or ribavirin in people with Hepatitis C, Chronic as compared to genotypes CT + TT.
Notes: Treatment was with peginterferon - the type not specified.  The association was with SVR(sustained virological response) [undetectable levels of HCV RNA 24 weeks after end of treatment].
Article: The Missing Association: Sequencing-Based Discovery of Novel SNPs in VKORC1 and CYP2C9 That Affect Warfarin Dose in African Americans
Gene: CYP2C9
Variant/haplotype: rs7089580
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin.
Article: Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort
Gene: AMHR2
Variant/haplotype: rs784892
Drug(s): metformin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with exposure to metformin as compared to allele G.
Article: The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions
Gene: CYP2D6
Variant/haplotype: rs16947
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with increased concentrations of clozapine in people with Schizophrenia as compared to genotypes AA + AG.
Notes: Alleles complemented. "Compared with the corresponding groups, the clozapine plasma concentrations of individuals with the *10TT genotype and individuals with the *2CC genotype were the highest (P < .05). "
Article: Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady‐state disposition of lamotrigine in adults with epilepsy
Gene: UGT1A4
Variant/haplotype: rs2011425
Drug(s): lamotrigine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with concentrations of lamotrigine in people with Epilepsy as compared to allele T.
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP3A4
Variant/haplotype: CYP3A4 poor metabolizer and intermediate metabolizer genotypes
Drug(s): tamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A4 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of tamoxifen in women with Breast Neoplasms.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Variant/haplotype: rs6002616
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele G.
Article: Hispanic ethnicity and the rs4880 variant in SOD2 are associated with elevated liver enzymes and bilirubin levels in children receiving asparaginase-containing chemotherapy for acute lymphoblastic leukemia
Gene: SOD2
Variant/haplotype: rs4880
Drug(s): bilirubin
Phenotype category: Toxicity
Significant: yes
Association: Genotype GG is associated with increased concentrations of bilirubin in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AA + AG.
Notes: when treated with asparaginase. ALT and AST were also significantly elevated but it was not significantly associated with hepatotoxicity. Alleles complemented to plus chromosomal strand.
Article: Gender‐specific association between preproendothelin‐1 genotype and reduction of systolic blood pressure during antihypertensive treatment‐‐‐results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA)
Gene: EDN1
Variant/haplotype: rs5370
Drug(s): atenolol, irbesartan
Phenotype category: Efficacy
Significant: yes
Association: Genotype GT is associated with increased response to atenolol and irbesartan in men with Essential hypertension as compared to genotype GG.
Notes: Men with the GT genotype had a greater reduction in systolic blood pressure (SBP) between baseline and 12 weeks of treatment, as compared to those with the GG genotype. p-value was adjusted for age, dose, and SBP, diastolic blood pressure and left ventricular mass index (LVMI) at baseline.
Article: Novel genomic variants influencing methotrexate delayed clearance in pediatric patients with acute lymphoblastic leukemia
Gene: PKD1L2
Variant/haplotype: rs16954698
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased clearance of methotrexate in children with Acute lymphoblastic leukemia as compared to allele G.
Notes: "Of all three patients with PKD1L2 rs16954698, two had delayed MTX clearance with first infusion and one with the third infusion. Compared to the wild-types of this variant, heterozygotes showed statistically significantly worse status in all renal function indices such as Cr, eGFR, BUN, and grade ≥2 AKI after HD-MTX administration (Supplementary Table S5)." "Case (MTX, delayed clearance) was defined as serum MTX, level (μmol/L) at 24 h ≥ 15 or 48 h ≥ 1.5 or 72 h ≥ 0.15 or 168 h ≥ 0.1, otherwise defined as control."
Article: Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test
Gene: ATF2
Variant/haplotype: rs3845744
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to fentanyl in people with Pain, Postoperative as compared to allele T.
Article: Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): everolimus
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *3/*3 is not associated with metabolism of everolimus in people with Kidney Transplantation as compared to CYP3A5 *1/*1 + *1/*3.
Notes: No significant difference in dose-adjusted area under the blood concentration-time curve (AUC/D) or dose-adjusted trough concentration (C0/D) was seen between the genotypes either at 1 month (p=0.915 and p=0.816, respectively) or 1 year (p=0.708 and p=0.540, respectively) post-transplant. Everolimus was given on day 14 of tacrolimus treatment. Note that at 1 year post-transplant only 31 patients remained for analysis.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: AIDA
Variant/haplotype: rs2378597
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of vancomycin as compared to allele A.
Notes: The SNP was not associated with trough levels of vancomycin (first vancomycin trough documented in EMR after at least 3 doses vancomycin). Elimination constants were also calculated.
Article: Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway
Gene: FHIT
Variant/haplotype: rs49411
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to antidepressants in people with Depressive Disorder, Major as compared to allele T.
Notes: Identity of minor allele not specified, so minor allele of dbSNP used here. Response measured at >50% reduction in symptoms at discharge of the Hamilton Rating Scale for Depression (HRSD17). Patients measured at admission and discharge, 4-6 weeks later. Specific antidepressants not listed.
Article: Beneficial effect of ezetimibe-atorvastatin combination therapy in patients with a mutation in ABCG5 or ABCG8 gene
Gene: ABCG5
Variant/haplotype: ABCG5 deficiency
Drug(s): ezetimibe
Phenotype category: Efficacy
Significant: yes
Association: ABCG5 deficiency is associated with increased clinical benefit to ezetimibe in people with Familial hypercholesterolemia.
Notes: "ezetimibe-atorvastatin combination therapy might be more beneficial in hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene." Variants identified were c.348C > A (p.Asn116Lys),  c.635-1G > A, c.1166G > A (p.Arg389His), c.1673_1677delCTTTT (p.Pro558GlnfsTer14) (unable to map to ClinVar or dbSNP as this time)
Article: The role of candidate pharmacogenetic variants in determining valproic acid efficacy, toxicity and concentrations in patients with epilepsy
Gene: CYP2D6
Variant/haplotype: rs3892097
Drug(s): valproic acid
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with decreased clinical benefit to valproic acid in people with Epilepsy as compared to genotype CC.
Notes: "Carriers of rs3892097 (CYP2D6) constituted 26.67% of the treatment failure group compared to 14.15% of the treatment success group (p = 0.047). The multivariate OR adjusted for maintenance VPA dose was 0.389 [0.169; 0.894] (p = 0.026), indicating that patients experiencing treatment failure were approximately 2.5 times more likely to carry this polymorphism. This underscores the detrimental effect of rs3892097 (CYP2D6) on the success rate of VPA monotherapy. No other SNPs showed significant associations with treatment outcome (Figure 1; Supplementary Table S2)."
Article: Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): phenprocoumon
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 *2 + *3 are associated with decreased metabolism of phenprocoumon as compared to CYP2C9 *1.
Notes: Daily dose of phenprocoumon is not significantly associated with CYP2C9 genotype. Daily dose is negatively correlated with age. This study published an algorithm for daily dose that includes height, although height was not significant in univariate analysis. This haplotype is significantly associated with higher phenprocoumon concentration as compared to patients with the wildtype haplotype.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: SLC6A3
Variant/haplotype: rs6347
Drug(s): heroin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of heroin in people with Heroin Dependence as compared to allele T.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP2E1, DUX1
Variant/haplotype: rs2070673
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele A.
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.
Article: Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased concentrations of efavirenz in people with HIV Infections as compared to allele G.
Notes: When considered as part of a composite (rs3745274 T, rs28399499 C, and rs4803419 T), the T allele was strongly associated with plasma efavirenz concentrations (plasma [EFV]) [beta=0.28, 95% CI (0.21, 0.35) p=2.4 E-11]. In a final multivariable model  the T allele was associated with a 31% increased in plasma [EFV] (beta=0.27). Post-hoc sensitivity analysis, in which two extreme outliers were excluded from analysis (N=111), showed that the T allele was associated with a 33% increase in plasma [EFV]. Multi-level mixed effects models predicted plasma [EFV] as a function of 1) fixed age effect, time after dose, CYP2B6 composite genotype  T,C,T and 2) random effects of the individual to account for w/in individual correlations, the genotypes TT and GT were associated with a 2.9 fold increase in and a 1.5 fold increase in plasma [EFV], respectively.
Article: Effect of CYP3A4*22, CYP3A5*3, and CYP3A Combined Genotypes on Cyclosporine, Everolimus, and Tacrolimus Pharmacokinetics in Renal Transplantation
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): everolimus, tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A4 *1/*1 is not associated with clearance of everolimus or tacrolimus in people with Kidney Transplantation as compared to CYP3A4 *1/*22 + *22/*22.
Article: A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*9
Drug(s): noscapine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 *1/*1 + *1/*9 (assigned as normal metabolizer phenotype) is associated with increased clearance of Noscapine in healthy individuals as compared to CYP2C9 *1/*2 + *1/*3 + *2/*3 + *3/*3 (assigned as intermediate metabolizer and poor metabolizer phenotype) .
Notes: "Signifcant diferences; were observed only between genotype-predicted phenotype; groups of CYP2C9 when comparing Cmax (p values, 0.00091; and 0.00013) and AUC0–t; (p values, 0.0047 and 0.00096) for; EMs with IMs (AS of 1.5) and EMs with PMs & IMs (AS; of 1.0), respectively."
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: rs397515874
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 Leu243Phe.
Article: Adiponectin Gene Polymorphism rs2241766 T/G Is Associated with Response to Pioglitazone Treatment in Type 2 Diabetic Patients from Southern China
Gene: ADIPOQ
Variant/haplotype: rs2241766
Drug(s): pioglitazone
Phenotype category: Efficacy
Significant: yes
Association: Genotype GT is associated with increased response to pioglitazone in people with Diabetes Mellitus as compared to genotype TT.
Notes: Response was defined as "any decrease greater than (or equal to) 15%" of glycated hemoglobin (HbA1C%).  When comparing the response rates between patients with the GT versus TT genotypes, the GT genotypes were associated with a greater frequency of response (52.94% versus 12.7% p=0.001) as well as a greater decrease in HbA1c% as compared to patients with the TT genotype (1.15 versus 0.52 p=0.001). Logistic regression analysis showed that rs2241766 GT genotype was associated with response to pioglitazone. *Please note: there were no individuals of genotype GG.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: DRD2
Variant/haplotype: rs1800497
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to risperidone in people with Schizophrenia as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin
Gene: SCN1A
Variant/haplotype: rs3812718
Drug(s): carbamazepine
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with increased dose of carbamazepine in people with Epilepsy as compared to genotype CC.
Article: Race influences warfarin dose changes associated with genetic factors
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*2 + *2/*2 are associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: only in European Americans, but not African Americans. (20.6% vs 3.0% dose reduction per variant allele, interaction p value<0.001)
Article: Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation
Gene: CFTR
Variant/haplotype: rs77010898
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to ivacaftor in people with Cystic Fibrosis as compared to genotype GG.
Notes: This study was a cell study and a case report of a woman with AA genotype. FEV1 did not improve, but ivacaftor was associated with better weight gain and fewer months with exacerbations.
Article: Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis
Gene: TRAF3IP2
Variant/haplotype: rs33980500
Drug(s): etanercept
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to etanercept in people with Arthritis, Rheumatoid as compared to allele C.
Notes: At six months after beginning treatment, a significant association between rs33980500 and decreased response to TNF inhibitors (i.e. etanercapt and adalimumab) in terms of the number of patients in remission (p=0.02, OR=0.09, C.I.=0.01-0.70) or with low disease activity (p=0.013, OR=0.1, C.I.=0.02-0.87) was seen across the whole cohort, but was not seen at two years after beginning treatment and could not be replicated in the subgroups for each individual drug.
Article: Pharmacogenetic Predictors of Statin-Mediated Low-Density Lipoprotein Cholesterol Reduction and Dose Response
Gene: ABCA1
Variant/haplotype: rs12003906
Drug(s): atorvastatin, pravastatin, simvastatin
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to atorvastatin, pravastatin or simvastatin in people with Hyperlipidemias as compared to allele G.
Notes: As measured by reduction in LDLc. Association was seen at low and high doses. Association reported for minor allele but base not specified; estimated from dbSNP to be the C allele (on the plus chromosomal strand).
Article: PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients
Gene: NR1I2
Variant/haplotype: rs6785049
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AG 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 GG and AG genotypes of this SNP.
Article: A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients
Variant/haplotype: rs12777823
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased metabolism of warfarin in people with Atrial Fibrillation, venous thromboembolism or Heart Valve Diseases as compared to allele G.
Notes: for S-warfarin stereoisomer in particular, measured as increased S-warfarin/R-warfarin ratio and decreased S-7OH-warfarin/S-warfarin and using a Bonferroni-adjusted replication significance threshold p < 3.21 × 10−4.
Article: CYP2C8*3 predicts benefit/risk profile in breast cancer patients receiving neoadjuvant paclitaxel
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): paclitaxel
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CT are not associated with increased response to paclitaxel in women with Breast Neoplasms as compared to genotype TT.
Notes: Response = complete clinical response (cCR). Some patients who had HER2 overexpressing tumors received trastuzumab at the same time as the paclitaxel. Also reported as CYP3A4*1B.