shlokn/autogkb huggingface dataset:
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Gene: PRKCA
Variant/haplotype: rs16960228
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele G.
Notes: Observations: 4.46 mm Hg increased reduction of diastolic blood pressure per A allele in PEAR + GERA, 3.26 mm Hg increased reduction of diastolic blood pressure per A allele in NORDIL, and 4.16 mm Hg increased reduction of diastolic blood pressure per A allele in PEAR + GERA + NORDIL.The association did not reach genome-wide significance when only PEAR + GERA were analyzed, but this SNP was selected for replication in NORDIL and here the association reached significance.  It did not reach genome-wide significance  in the meta-analysis of PEAR + GERA + NORDIL.  It was then tested for replication in the GENRES and Milan cohorts, reaching significance in GENRES but not in the Milan cohort.
Article: ABCC3 Genetic Variants are Associated with Postoperative Morphine-induced Respiratory Depression and Morphine Pharmacokinetics in Children
Gene: ABCC3
Variant/haplotype: rs4793665
Drug(s): morphine-3-glucuronide, morphine-6-glucuronide
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased concentrations of morphine-3-glucuronide and morphine-6-glucuronide in children with Scoliosis or tonsillectomy as compared to genotypes CT + TT.
Article: Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European American and African Americans
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*5, CYP2C9*6, CYP2C9*11
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *2 + *3 + *5 + *6 + *11 are associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: in European Americans.
Article: The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients
Gene: SLC47A1
Variant/haplotype: rs2289669
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotypes AA + AG.
Notes: Looked at changes in the following as measures of metformin response between AA/GA (n=50) and GG genotype (n=3): fasting blood glucose (p=0.112), postprandial blood glucose (p=0.171), fasting insulting (p=0.015), postprandial insulin (p=0.259), glycosylated hemoglobin (p=0.227), triglycerides (p=p=0.434), total cholesterol (p=0.224), low-density lipoprotein (p=0.451), high-density lipoprotein (p=0.399), homeostasis model assessment of insulin resistance (p=0.081), homeostasis model assessment of insulin sensitivity (p=0.001), homeostasis model assessment of B cell function (p=0.493), and quantitative insulin sensitivity check index (p=0.002). Also, found an interaction between this SNP and SLC47A1 rs2289669, with patients with rs594709 AA genotypes and rs2289669 AA genotypes showing higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p-0.014) than patients with rs2289669 GA or GG genotypes. Patients with rs594709 G allele carriers and also rs2289669 AA genotype showed greater decrease in TChol (p=0.013) than GA or GG genotypes.
Article: Genome-Wide Analysis of Clopidogrel Active Metabolite Levels Identifies Novel Variants that Influence Antiplatelet Response
Variant/haplotype: rs9732195
Drug(s): clopidogrel thiol metabolite H4
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is associated with concentrations of clopidogrel thiol metabolite H4 in healthy individuals as compared to allele G.
Notes: In this GWAS, locus on chromosome 10 near the CYP2C9-CYP2C18-CYP2C19 gene cluster was significantly associated with active metabolite concentration; (rs137891020, P =9.5 × 10–15,according to dbSNP: rs137891020 has merged into rs9732195). This variant is non-significant after adjusting for CYP2C19*2 SNV.
Article: Association of Common C-Reactive Protein (CRP) Gene Polymorphisms With Baseline Plasma CRP Levels and Fenofibrate Response
Gene: CRP
Variant/haplotype: rs3093059
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to fenofibrate in people with Metabolic Syndrome as compared to genotypes AG + GG.
Notes: No significant difference in the change of C-reactive protein (CRP) levels between baseline and 3 weeks of treatment, was seen between genotypes. In strong linkage disequilibrium with rs3091244 (r2 = 0.935, p < 0.001) and in weak linkage disequilibrium with rs1417938 and rs1205 (r2 = 0.17, p < 0.05).
Article: Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*46 + *46/*46 are associated with increased metabolism of nicotine as compared to CYP2A6 *1/*1.
Notes: Please note that the *46 allele is described as the *1B1 allele in the paper and has subsequently been reassigned by PharmVar.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DBH
Variant/haplotype: rs1611114
Drug(s): heroin
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of heroin in people with Heroin Dependence as compared to allele C.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: ABCG2
Variant/haplotype: rs45499402
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to allopurinol.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment. This SNP is in perfect LD with rs2231142.
Article: Effects of CYP2C19 Loss-of-Function Variants on the Eradication of H. pylori Infection in Patients Treated with Proton Pump Inhibitor-Based Triple Therapy Regimens: A Meta-Analysis of Randomized Clinical Trials
Gene: CYP2C19
Variant/haplotype: CYP2C19*1
Drug(s): esomeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *1/*1 is not associated with response to esomeprazole in people with Helicobacter Infections.
Notes: as compared to the *1/*2 or *1/*3 genotype, or the *2/*2, *2/*3 or *3/*3 genotype. No significant differences in eradication rate of Helicobacter pylori (H. pylori) were seen between any of the genotype groups.This was a meta-analysis and included 4 studies. Patients were treated with the drugs anywhere from 7-14 days, and also received the antibiotics amoxicillin and clarithromycin or amoxicillin and levofloxacin as part of triple therapy.
Article: ABCB1 Genotype is Associated with Fentanyl Requirements in Critically Ill Children
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): fentanyl
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of fentanyl in children as compared to allele A.
Notes: No significant difference in fentanyl infusion dose between genotype groups.
Article: Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): tacrolimus
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to tacrolimus in people with Nephrotic Syndrome as compared to allele C.
Notes: This variant did not affect the clinical efficacy of tacrolimus. Effective response included patients with complete or partial remission, and ineffective response included patients with no remission or recurrence. The publication reports the finding for CYP3A4*1G. PharmVar re-assigned CYP3A4*1G to CYP3A4*36. Previously, this annotation used CYP3A4*36 which has been retired by PharmVar. All references to *36 have been replaced by rs2242480 alleles.
Article: Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta‐Analysis
Gene: SLC47A2
Variant/haplotype: rs12943590
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.
Notes: This variant is not associated with metformin glycemic response assessed as HbA1c reduction in patients on metformin monotherapy.
Article: Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients
Gene: AMPD1
Variant/haplotype: rs17602729
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele G.
Article: Sex‐Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans
Gene: SLC22A1
Variant/haplotype: SLC22A1 deficiency
Drug(s): berberine
Phenotype category: Metabolism/PK
Significant: no
Association: SLC22A1 deficiency is not associated with decreased concentrations of berberine in healthy individuals as compared to SLC22A1 normal metabolizer.
Notes: "No significant differences were observed in berberine plasma con-centrations or AUC 0–48h between poor OCT1 transporters, poorCYP2D6 metabolizers, and the reference group (Figure 4a,b,Table 1)." "Poor OCT1 transporters were defined as homozygous or compound het-erozygous carriers of OCT1 alleles *3, *4, *5, or *6. " "OCT1 alleles *1 (reference allele), *2 (Met420del),*3 (Arg61Cys), *4 (Gly401Ser), *5 (Gly465Arg, Met420del), *6 (Cys88Arg, Met420del)"
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs524731
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele C.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG are associated with increased concentrations of tacrolimus in people with lung transplantation as compared to genotype GG.
Notes: Alleles given as the reverse strand C and T. Concentrations measured as trough blood drug concentrations. Differences in concentrations between CT and CC patients were seen 6 months after transplant.
Article: CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*5, CYP2D6*10
Drug(s): dextromethorphan
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *5/*10 is associated with decreased metabolism of dextromethorphan in healthy individuals as compared to CYP2D6 *1/*1 + *1/*10 + *10/*10.
Notes: Single dose study with 15mg dextromethorphan DM. Urine, Plasma, and Saliva Metabolic Ratios were accessed. Subjects were  genotyped by DNA sequencing analysis for CYP2D6*1, *2, *3, *4, *6, *7, *10, *14, *18, *21, *28, *33, *34, *35, *36, *39, *41, *43, *49, *51, *52, *54, *60, *63, *65, *69, *71, and *75 and CNV were determined. NM n= 190; *5/*10 n=35. The urinary, plasma, or salivary MRs increased successively in subjects with CYP*1/*1, *1/*10, *10/*10, and *5/*10 with statistical significance (all P-values < 0.001).
Article: Methadone pharmacogenetics: CYP2B6 polymorphisms determine plasma concentrations, clearance and metabolism
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *1/*6 + *6/*6 is associated with decreased clearance of methadone in healthy individuals as compared to CYP2B6 *1/*1.
Notes: PK measures were AUC, clearance, peak concentration, exposure.
Article: Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770
Gene: CFTR
Variant/haplotype: rs75527207
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to ivacaftor.
Notes: In vitro assays that show ivacaftor potentiates CFTR with the G551D mutation (rs75527207 allele A) - see details described in study parameters.
Article: Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: not stated
Association: Genotype GG is associated with decreased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity.
Notes: Using multiple logistic regression analysis to examine the relationship between various clinical parameters and treatment response showed that ADRA2A GG genotype (OR=5.6), the presence of a psychiatric comorbidity (OR=5.6) and low SES (OR=2.3) were associated with reduced response to methylphenidate treatment.
Article: Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities
Gene: CYP2B6
Variant/haplotype: rs2279344
Drug(s): S-EDDP
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with concentrations of (S)-EDDP as compared to allele G.
Article: Genetic polymorphisms in the long noncoding RNA MIR2052HG offer a pharmacogenomic basis for the response of breast cancer patients to aromatase inhibitor therapy
Variant/haplotype: rs3802201
Drug(s): anastrozole, exemestane
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with increased response to anastrozole and exemestane in women with Breast Neoplasms as compared to allele G.
Notes: Patients included postmenopausal women with resected stage I–III breast cancer that was ERa and/or PgR positive and randomized to five years of anastrozole or exemestane. Did not reach statistical significance for GWAS (P<5 x 10^-8).
Article: Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: a prospective study
Gene: VKORC1
Variant/haplotype: rs2359612
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with decreased dose of warfarin as compared to allele G.
Article: Genome-wide association analysis of anti-TNF drug response in rheumatoid arthritis patients
Gene: CNTN5
Variant/haplotype: rs1813443
Drug(s): Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to allele G.
Notes: This is one of three SNPs that showed directional consistency of association in 4 cohorts studied, along with improved  p value in a 3 stage meta-analysis compared to the first GWAS stage.  Since this is a CG SNP, the associated allele may be incorrect; it was reported as C and the SNP is in +-strand gene. p did not reach genome-wide significance.
Article: Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment
Gene: NPC1L1
Variant/haplotype: rs2072183
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to hmg coa reductase inhibitors in people with Cardiovascular Diseases and Hypercholesterolemia as compared to allele C.
Notes: as measured by lesser reductions in LDL-C. These individuals were also more likely to start out with higher LDL-C before treatment. NPC1L1 is on the minus strand therefore alleles were complemented and shown here on plus chromosomal strand. Paper shows C as effect allele and also minor allele in European-ancestry individuals.
Article: Evaluation of the role of metabolizing enzymes and transporter variants in ezetimibe pharmacokinetics
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): ezetimibe
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is associated with decreased dose-adjusted trough concentrations of ezetimibe in healthy individuals as compared to genotypes CC + TT.
Notes: Alleles complemented. "A tendency towards higher Cmax/DW in ABCB1 rs2032582 G/G; + A/A+ G/A subjects compared to ABCB1 T/T (p univariate (puv) =; 0.056, p multivariate (pmv) = 0.049, β = 0.243, R2 = 0.067) (Table 4)" This is a trialleleic and difficult to represent in the structured sentence. Table 4 shows allele frequencies for "TT n=17, T/G + T/A 28, G/G + A/A+ G/A 50"
Article: Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*3 is associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: In this meta-analysis of warfarin Dose in Black-African Patients, CYP2C9*3 allele is associated with 12.5mg/week less warfarin dose requirement compared to wild-type homozygotes.
Article: Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): donepezil
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with clearance of donepezil in people with Alzheimer Disease as compared to genotype CC.
Notes: Genotypes of CYP3A4*1B TT, AC and CC did not influence donepezil clearance in a covariate model. Alleles have been complemented to the plus chromosomal strand.
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs4580760
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to olanzapine in people with Schizophrenia as compared to genotypes AA + AC.
Notes: Not significant after correction for multiple testing using the False Discovery Rate. Response was assessed by change in the total Positive and Negative Syndrome Scale (PANSS) score.
Article: Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
Gene: SCN9A
Variant/haplotype: rs6746030
Drug(s): propofol
Phenotype category: Other
Significant: yes
Association: Genotypes AA + AG are associated with increased response to propofol as compared to genotype GG.
Notes: The AA and AG genotypes were associated with lower BIS values, indicating increased susceptibility to propofol compared to the GG genotypes (51.13±15.37 vs. 61.30±10.39). Please note: the authors examined 58 SNPs but did not do multiple testing corrections.
Article: The OPRD1 rs678849 variant influences outcome of disulfiram treatment for cocaine dependency in methadone-maintained patients
Gene: OPRD1
Variant/haplotype: rs678849
Drug(s): disulfiram
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to disulfiram in people with Cocaine-Related Disorders as compared to genotypes CT + TT.
Notes: Patients with the CC genotype had a significantly reduced number of cocaine-positive urine samples when treated with disulfiram.
Article: CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): esomeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *17 is not associated with response to esomeprazole in children with eosinophilic esophagitis as compared to CYP2C19 *1/*1.
Notes: carriage of CYP2C19􏰀17 GOF was not associated with either PPI-REE or complete PPI-REE outcomes in the non-pH cohort (PPI-REE OR [95% CI] = 1.38 [0.34,5.61], P = 0.65; complete PPI-REE OR =1.54 (0.37-6.46) p=0.56
Article: Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population
Gene: AGTR1
Variant/haplotype: rs5186
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AC is associated with increased exposure to atorvastatin in healthy individuals as compared to genotypes AA + CC.
Notes: AUC (0-time t) and AUC (0-infinity) values were significantly higher in the AC genotype (186.44±92.45 and 204.55±94.76 ng/ml/h, respectively) vs the CC genotype (95.57±43.10 and 109.28±40.84 ng/ml/h) (P<0.05 each) as well as when compared to AA + CC genotypes combined (159.28±79.71 ng/ml/h) (P<0.05). Clearance was significantly lower in the AC genotype (473.67±220.44 l/h) vs CC (810.19±275.81 l/h) or vs. AA+CC (614.68±277.11 l/h); (P<0.05). Genotype was not associated with half-life, Cmax, or elimination rate constant of atorvastatin.
Article: Pharmacogenetic Influence of LOC387715/HTRA1 on the Efficacy of Bevacizumab Treatment for Age-Related Macular Degeneration in a Korean Population
Gene: ARMS2
Variant/haplotype: rs10490924
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GT + TT are associated with increased response to bevacizumab in people with Macular Degeneration as compared to genotype GG.
Notes: Patients with the GT and TT genotype had greater improvements in visual acuity (using a Snellen eye exam chart then converted to a logarithm of the minimal angle of resolution value) between baseline and 6 months of treatment, as compared to those with the GG genotype. Patients with the TT genotype had the greatest visual acuity improvement, followed by the GT and then the GG genotype. No significant differences were seen when considering improvement over 12 months of treatment.
Article: Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population
Gene: CHRNA5
Variant/haplotype: rs16969968
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele A is not associated with exposure to nicotine in men as compared to allele G.
Notes: The A allele was initially associated with an increased likelihood of being a smoker but this lost significance following correction for multiple testing.
Article: ABCC2 Polymorphisms and Haplotype are Associated with Drug Resistance in Chinese Epileptic Patients
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with increased resistance to antiepileptics in people with Epilepsy as compared to allele G.
Article: Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a randomized placebo-controlled trial
Gene: CHRNA5
Variant/haplotype: rs16969968
Drug(s): nicotine
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to nicotine in people with Tobacco Use Disorder.
Notes: compared to placebo. In African American smokers, combination nicotine replacement therapy (patch and lozenge) was more effective in smokers with rs16969968 GG genotype than was placebo. There was no significant genotype-by-treatment interaction in smokers of European ancestry.