shlokn/autogkb huggingface dataset:
Article: Sulfasalazine disposition in a subject with 376C>T (nonsense mutation) and 421C>A variants in the ABCG2 gene
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): sulfasalazine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype TT is associated with decreased clearance of sulfasalazine in healthy individuals as compared to genotypes GG + GT.
Notes: The mean AUC(0,48 h) was 3-fold higher and Cmax was 2.5-fold higher in individuals with the TT genotype as compared to individuals with the GG genotype. The apparent oral clearance (dose/ AUC(0,48 h)) was 3-fold lower in individuals with the TT genotype as compared to individuals with the GG genotype. The authors reported no differences in sulfasalazine PK between the GG genotype and GT genotype, however a single individual was compound heterozygous at rs72552713 (CT) and rs2231142 (GT) in and altered PK as compared to other individuals who were heterozygous only at rs2231142 (GT). Please note: alleles have been complemented to the + chromosomal strand.
Article: Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population
Gene: SLC15A2
Variant/haplotype: rs1143671
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of warfarin as compared to genotype CC.
Article: Genome-wide study of methotrexate clearance replicates SLCO1B1
Gene: SLCO1B1
Variant/haplotype: rs4149081
Drug(s): methotrexate
Phenotype category: Efficacy, Toxicity, Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
Article: RHOA Is a Modulator of the Cholesterol-Lowering Effects of Statin
Gene: RHOA
Variant/haplotype: rs11716445
Drug(s): pravastatin, simvastatin
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to pravastatin or simvastatin in people with Hypercholesterolemia as compared to allele G.
Notes: The associated effect was on LDL Cholesterol and explained less than 1% of the variation.
Article: Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine
Gene: KCNMB1
Variant/haplotype: rs11739136
Drug(s): dexmedetomidine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to dexmedetomidine in people with surgery as compared to genotype TT.
Notes: as measured by shorter onset time. "In our study, carriers of the minor allele (CT/TT) needed a shorter onset time than homozygous carriers of the major allele (CC) (16.60 ± 15.42 vs. 23.91 ± 16.47, p = 0.009). Therefore, heterozygosity or homozygosity for the minor allele T) of KCNMB1 rs11739136 resulted in more sensitizing to DXM sedation."
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 A 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: Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with dose of warfarin in children as compared to genotype TT.
Article: Significance of CYP3A4∗1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): sufentanil
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with increased dose of sufentanil in women with Pain, Postoperative as compared to genotypes CT + TT.
Notes: rs2242480 is the defining allele for CYP3A4*36. The publication reports the finding for CYP3A4*1G. PharmVar re-assigned CYP3A4*1G to CYP3A4*36.
Article: PHARMACOGENOMIC GENOME-WIDE META-ANALYSIS OF BLOOD PRESSURE RESPONSE TO BETA-BLOCKERS IN HYPERTENSIVE AFRICAN AMERICANS
Gene: ZMAT4
Variant/haplotype: rs1367094
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to atenolol or metoprolol in people with Hypertension as compared to allele C.
Notes: In African Americans.; Association found in atenolol and metoprolol monotherapy, but not validated in a atenolol plus hydrochlorothiazide therapy
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP3A4
Variant/haplotype: rs35599367
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 variant passed validation the EA population but frequency was too low in AA population to test. Direction of effect was not stated.
Article: Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation
Gene: VKORC1
Variant/haplotype: rs8050894
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele G is associated with decreased dose of warfarin as compared to allele C.
Article: Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo
Gene: CYP3A4
Variant/haplotype: CYP3A4*22
Drug(s): risperidone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A4 *22 is not associated with decreased clearance of risperidone.
Notes: "CYP3A4*22 was; not significant as a covariate in the model (p=0.31)."
Article: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR
Gene: CFTR
Variant/haplotype: rs75527207
Drug(s): ivacaftor, tezacaftor
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with response to ivacaftor and tezacaftor in people with Cystic Fibrosis.
Notes: G551D allele. Significant improvements in sweat chloride level, ppFEV1 and CFQ-R scores were observed in the efficacy testing phase.
Article: VKORC1 variants as significant predictors of warfarin dose in Emiratis
Gene: VKORC1
Variant/haplotype: rs7294
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: Please note that alleles have been complemented to the positive strand.
Article: Polymorphism at position –308 of the tumour necrosis factor α gene and rheumatoid arthritis pharmacogenetics
Gene: TNF
Variant/haplotype: rs1800629
Drug(s): infliximab
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to infliximab in people with Arthritis, Rheumatoid as compared to genotype AG.
Notes: Patients with the GG genotype had a significantly greater decrease in the Disease Activity Score in 28 joints (DAS28) score as compared to those with the AG genotype (no patients with the AA genotype were present in the cohort) after a mean of 24.8 months of treatment. The authors also noted a tendency of a better Health Assessment Questionnaire (HAQ) evolution (p=0.064), but no significant difference in radiological outcome (Sharp score).
Article: Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention
Gene: HNF1B
Variant/haplotype: rs11868513
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to metformin as compared to genotype GG.
Notes: Subjects were at high risk of diabetes and were recruited from Diabetes Prevention Program (DPP) and were followed for a year. The authors measured changes in response to insulin at baseline and one year after treatment. Subjects with the AA genotypes had the highest diabetes incidence in the placebo group but had a significant response to metformin. Subjects with the AG genotype had lower diabetes incidence rates than subjects with the AA genotype, but incidence of diabetes were significantly associated with lifestyle changes or metformin. Diabetes incidence rates were lower in subjects with the GG genotype with lifestyle intervention (P<0.001) but not by metformin (P=0.2) as compared with placebo.
Article: Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma
Gene: CLCN6, MTHFR
Variant/haplotype: rs1801133
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with concentrations of methotrexate in children with Osteosarcoma as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): hydralazine
Phenotype category: Metabolism/PK
Significant: not stated
Association: NAT2 slow acetylator is associated with decreased metabolism of hydralazine in people with Neoplasms as compared to NAT2 rapid acetylator.
Notes: Note, NAT2 not specified just categorized in slow and rapid acetylator. Patients received a single oral 500-mg dose (two 250-mg tablets) of sulfamethazine and urine was collected within the ensuing 6 h for acetylator status phenotyping. Afterward, patients began treatment (day –7) with a daily dose of a slow-release formulation of hydralazine tablets containing either 182 mg for rapid-acetylators or 83 mg for slow- acetylators. Plasmatic levels of hydralazine were analyzed in 10 patients in whom plasma samples were available at different time-points during treatment. Distribution of these patients according to acetylator phenotype was four and six for slow and rapid, respectively. Mean plasma levels of hydralazine ranged from 204.8–275.1 ng/mL for rapid-acetylators, whereas these mean values were 252.1–344.2 ng/mL in slow- acetylators. Overall means were 246 and 299 ng/mL, respectively, which were not statistically significant different (p = 0.2445). The subjects received also other drugs to treat neoplasms.
Article: Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma
Gene: C6
Variant/haplotype: rs3805716
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with dose-adjusted trough concentrations of tacrolimus in people with liver transplantation as compared to genotypes AT + TT.
Notes: No significant difference was seen when considering DONOR genotype at week 4 of treatment. Patients with hepatocellular carcinoma.
Article: Germline Polymorphisms as Biomarkers of Tumor Response in Colorectal Cancer Patients Treated with Anti-EGFR Monoclonal Antibodies: A Systematic Review and Meta-Analysis
Gene: CXCL8
Variant/haplotype: rs4073
Drug(s): cetuximab, panitumumab
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to cetuximab or panitumumab in people with Colorectal Neoplasms as compared to allele A.
Notes: Meta-analysis with 3 studies. The authors did not provide the exact number of patients but stated that "the median number of patients per analysis was 110 (range 50 - 740)". Most definitions of response were variations of the RECIST criteria.
Article: The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): cyclophosphamide
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased clinical benefit to cyclophosphamide in people with Leukemia, Lymphocytic, Chronic, B-Cell as compared to genotypes GT + TT.
Notes: " In contrast to patients with the GG genotype, who were classified as 83% responders, 14.5% non-responders, and 2.5%) no responders, patients carrying variant genotypes (GT + TT) were classified as (37.5% responders, 58.5% non-responders, and 4% toxic death). Based on the data in Table S2, we found that there was a significant (p < 0.001) association between the variant genotypes and response failure."
Article: Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotypes CT + TT.
Notes: The dose-adjusted trough concentrations of tacrolimus on the first day of tacrolimus administration (pre-transplantation) was 70% higher for those with the CC genotype ("poor metabolizers") as compared to those with the CT or TT genotype ("extensive metabolizers").
Article: Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states1
Gene: GCKR
Variant/haplotype: rs780094
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: not stated
Association: Genotypes CT + TT are associated with increased response to fenofibrate in people with Hypertriglyceridemia.
Notes: When combined with EITHER rs662799 AG + GG genotypes, OR rs3135506 CG + GG genotypes. This combined genotype group is associated with a greater reduction in triacylglycerol concentrations between baseline and 3 weeks of treatment, as compared to any other genotype combination. Adjusted for baseline triacylglycerol.
Article: Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease
Gene: PON1
Variant/haplotype: rs662
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to clopidogrel in people with Coronary Artery Disease as compared to allele C.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: ESYT2
Variant/haplotype: rs1061735
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Effects of Cytochrome P450 2C19 and Paraoxonase 1 Polymorphisms on Antiplatelet Response to Clopidogrel Therapy in Patients with Coronary Artery Disease
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *2 is associated with decreased response to clopidogrel in people with Coronary Artery Disease as compared to CYP2C19 *1.
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: SNAP25
Variant/haplotype: rs3746544
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GG + GT are associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotype TT.
Notes: For the genetic component, in the CGI-S model, a dominant effect in SNAP25 rs3746544 was found with a significant improvement in the symptoms. Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).
Article: Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort
Gene: VDR
Variant/haplotype: rs11168293
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with increased dose of warfarin as compared to genotypes GG + GT.
Notes: This SNP is in very tight linkage disequilibrium with rs11168292 and rs4760658 (r2>0.97). Mean dose (in mg) of warfarin according to genotype was: TT>GT>GG. p-value adjusted for CYP2C9 metabolizer status and VKORC1 activity status phenotypes, among other factors. Warfarin dose requirement was defined as the reported daily dose at 3 months following treatment initiation.
Article: Discordant Associations between SLCO1B1 521T→C and Plasma Levels of Ritonavir-boosted Protease Inhibitors in AIDS Clinical Trials Group Study A5146
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): saquinavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with trough concentration of saquinavir in people with HIV Infections as compared to allele T.
Article: Impact of IL6R genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis
Gene: IL6R
Variant/haplotype: rs4845625
Drug(s): sarilumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to sarilumab in people with Arthritis, Rheumatoid as compared to genotypes CT + TT.
Notes: "Patients carrying the CC genotype for rs4845625 had worse response rates to sarilumab as measured by CDAI and DAS28 LDA rates (45.5% and 52.4% vs. 76.7% and 80% in the CT + TT genotypes, respectively; p = 0.021 and p = 0.037)."
Article: Effect of genetic variation in UGT1A and ABCB1 on moxifloxacin pharmacokinetics in South African patients with tuberculosis
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28, UGT1A1*36, UGT1A1*37
Drug(s): moxifloxacin
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A1 *1/*36 is associated with decreased clearance of moxifloxacin in people with Tuberculosis as compared to UGT1A1 *1/*1 + *1/*28 + *28/*28 + *28/*37.
Notes: "Having the TA 5/6 repeat in rs8175347 was associated with a 20.6% lower clearance and approximately 26% higher AUC, after adjusting for other covariates (such as efavirenz and/or rifampicin co-administration) compared with those with TA 6/6, 6/7, 7/7 and 7/8"
Article: RUNX transcription factors: association with pediatric asthma and modulated by maternal smoking
Gene: RUNX1
Variant/haplotype: rs11702779
Drug(s): methacholine chloride
Phenotype category: Other
Significant: yes
Association: Genotype AA is associated with increased response to methacholine chloride in children with Asthma as compared to genotypes AG + GG.
Notes: This is for children without prenatal tobacco exposure.
Article: Inherited NUDT15 Variant Is a Genetic Determinant of Mercaptopurine Intolerance in Children With Acute Lymphoblastic Leukemia
Gene: NUDT15
Variant/haplotype: rs116855232
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CC + CT.
Notes: Decreased dosage was likely to be due to increased toxicity. The authors also calculated a genetic risk score based on genotype at rs1142345 and at rs116855232. Patients who were homozygous wild-type at both SNPs had the lowest genetic risk score and patients who were homozygous for the variant allele at either SNP had the highest genetic risk score. There was an inverse significant association between genetic risk score and dose reduction of mercaptopurine.
Article: COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial
Gene: COMT
Variant/haplotype: rs4680
Drug(s): propranolol
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is associated with increased response to propranolol in people with Temporomandibular joint-pain-dysfunction syndrome as compared to genotype AA.
Notes: More patients with the GG genotype reported a ≥30% reduction in facial pain index at week 9 of treatment than AA patients. However, this association was not significant.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs145157460
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele T is associated with decreased metabolism of nicotine as compared to allele G.
Notes: Assigned as loss-of-function following in vitro assessments, in vivo associations and variant construct functional assignments. Please note that alleles have been complemented to the positive strand.
Article: Effect of the VKORC1 D36Y variant on warfarin dose requirement and pharmacogenetic dose prediction
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with increased dose of warfarin in people with warfarin maintenance treatment as compared to allele T.
Article: A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers
Gene: GRIK1
Variant/haplotype: rs2832407
Drug(s): topiramate
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AC is associated with increased concentrations of topiramate in people with Alcohol-Related Disorders as compared to genotype CC.
Notes: 75.5% of participants met the criteria for an alcohol use disorder. At target dose (week 5 of treatment), carriers of the A allele had higher serum topiramate levels as compared to those with the CC genotype. No association was seen with dose.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: FARP2
Variant/haplotype: rs757978
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.