shlokn/autogkb huggingface dataset:
Article: Genetic variants related to successful migraine prophylaxis with verapamil
Gene: PCDHB6
Variant/haplotype: rs17844444
Drug(s): verapamil
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased clinical benefit to verapamil in people with Migraine NOS as compared to allele G.
Notes: "There are 3 highly significant SNPs (p‐value < 0.008) in both the arithmetic and percentage change models: rs2230433 within the Integrin Subunit Alpha L gene (ITGAL) [OMIM#153370], rs17844444 in Protocadherin Beta 6 gene (PCDHB6) [OMIM#606332] and rs3733694 in Protocadherin Beta 7 gene (PCDHB7) [OMIM#606333]." "rs17844444 (PCDHB6) and rs3733694 (PCDHB7), the minor alleles predicted non‐response to verapamil."
Article: The Contribution of Common CYP2A6 Alleles to Variation in Nicotine Metabolism Among European Americans
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*9, CYP2A6*12, CYP2A6*38, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1 + *9 + *12 + *38 are associated with decreased metabolism of nicotine as compared to CYP2A6 *46.
Notes: Note that this study uses the *1B allele as the 'reference allele' (subsequently reassigned as the *46 allele by PharmVar) and that the *38 allele is described in the paper as '*1D-Y351H'.
Article: CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 are associated with increased dose of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: Mean starting dose was 45.96% higher in *1 carriers than in *3/*3 patients. One-year mean dose was 85.55% higher in *1 carriers compared to *3/*3.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Gene: PHACTR1
Variant/haplotype: rs4615376
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele A.
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: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs1063320
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotypes CG + GG.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). Neither were significantly associated with any genotype.
Article: VKORC1 variants as significant predictors of warfarin dose in Emiratis
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of warfarin as compared to genotype CC.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: SLCO1B3
Variant/haplotype: rs7311358
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of tenofovir in people with HIV Infections as compared to allele G.
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: FBXL17
Variant/haplotype: rs4431329
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele A.
Notes: The SNP was discovered in two independent cohorts, although no SNPs reached genome wide significance. The authors then considered P<1 x10^-5 as a threshold for significance (based on the results from a Q-Q plot distribution reference line). Using this revised threshold the authors reported that this SNP was associated with a lower decrease in diastolic blood pressure after hydrochlorothiazide treatment.
Article: Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin dosage in Han-Chinese patients: A systematic review and meta-analysis
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with decreased dose of warfarin as compared to allele G.
Article: Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European American and African Americans
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG are associated with decreased dose of warfarin as compared to genotype GG.
Notes: in European Americans and African americans.
Article: Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery
Gene: UGT2B7
Variant/haplotype: rs6851533
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.
Notes: There was no significant difference in PPLpost-PPLpre between the genotype groups.
Article: Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women
Gene: CHRNA5
Variant/haplotype: rs2036527
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to bupropion, nicotine or varenicline in women with Tobacco Use Disorder as compared to genotype GG.
Notes: Women with the AA or AG genotypes were more likely to be abstinent from smoking at 6 months after starting pharmacotherapy for smoking cessation compared to those with the GG genotype.
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: SLIT1
Variant/haplotype: rs11189015
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele G.
Notes: The SNP was discovered in two independent cohorts, although no SNPs reached genome wide significance. The authors then considered P<1 x10^-5 as a threshold for significance (based on the results from a Q-Q plot distribution reference line). Using this revised threshold the authors reported that this SNP was associated with a lower decrease in systolic blood pressure after hydrochlorothiazide treatment.
Article: Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia
Gene: SLC19A1
Variant/haplotype: rs1051266
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Effect of CYP3A4*22, CYP3A5*3, and CYP3A Combined Genotypes on Cyclosporine, Everolimus, and Tacrolimus Pharmacokinetics in Renal Transplantation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with increased clearance of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: Carriers of the *1 allele had 53% higher clearance as compared with non-carriers. CYP3A5*3 explained 5.5% of the variability in tacrolimus clearance.
Article: Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma
Variant/haplotype: rs953977
Drug(s): montelukast
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with increased response to montelukast in people with Asthma as compared to allele G.
Notes: This allele showed a trend toward association but not at the genome wide significance level. Study Cohort: Discovery cohort (N=133): American Lung Association Asthma Clinical Research Center (ALA-ACRC)-supported trials, the Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial (LOCCS) and Effectiveness of Low Dose Theophylline as Add On Therapy for the Treatment of Asthma (LODO) trials. Replication cohort (N=184): Childhood Asthma Research and Education (CARE) Network- Characterizing the Response to a LT Receptor Antagonist and an Inhaled Corticosteroid and Pediatric Asthma Controller Trial (CLIC and PACT).
Article: Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort
Gene: SLC22A1
Variant/haplotype: rs34059508
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: Pharmacogenetics of Antiepileptic Drug Efficacy in Childhood Absence Epilepsy
Gene: CACNA1H
Variant/haplotype: rs61734410
Drug(s): ethosuximide
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased clinical benefit to ethosuximide in children with Epilepsy as compared to allele C.
Notes: as measured by minor allele (T) frequency in not–seizure‐free vs seizure-free children.
Article: The Relation Between CYP2C19 Genotype and Phenotype in Stented Patients on Maintenance Dual Antiplatelet Therapy
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): aspirin, clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to aspirin and clopidogrel in people with Coronary Artery Disease as compared to allele G.
Notes: These patients had coronary arterial stenting.  The comparison was that ADP-induced ex vivo platelet aggregation was higher in (AA + AG) compared to GG, but the template does not accommodate this.  *2 SNP.  [stat_test: chi-square]
Article: Absorption of Montelukast is Transporter Mediated: a Common Variant of OATP2B1 is Associated with Reduced Plasma Concentrations and Poor Response
Gene: SLCO2B1
Variant/haplotype: rs12422149
Drug(s): montelukast
Phenotype category: Efficacy, Metabolism/PK
Significant: yes
Association: Genotype AG is associated with decreased response to montelukast in people with Asthma as compared to genotype GG.
Notes: It's also associated with significantly reduced plasma concentration of monteleukast.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Gene: AFAP1L1
Variant/haplotype: rs1438692
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele G.
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: Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits
Gene: CYP1A1
Variant/haplotype: rs2472297
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype CT is associated with decreased dose-adjusted trough concentrations of clozapine in people with Tobacco Use Disorder as compared to genotype CC.
Notes: significance is only given for combination of both CYP1A rs2472297 C>T and NFIB rs28379954 T>C genotypes
Article: Low heritability in pharmacokinetics of talinolol: a pharmacogenetic twin study on the heritability of the pharmacokinetics of talinolol, a putative probe drug of MDR1 and other membrane transporters
Gene: ABCB5
Variant/haplotype: rs17143212
Drug(s): talinolol
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with clearance of talinolol in healthy individuals as compared to allele C.
Notes: This was a twin study of monozygotic and dizygotic twins.
Article: Association of corticotropin releasing hormone receptor 2 (CRHR2) genetic variants with acute bronchodilator response in asthma
Gene: CRHR2
Variant/haplotype: rs255100
Drug(s): salbutamol
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with decreased response to salbutamol in people with Asthma as compared to allele T.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: DRD2
Variant/haplotype: rs1799978
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to risperidone in people with Schizophrenia as compared to allele T.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Population Pharmacokinetics and Pharmacogenetics Analysis of Rilpivirine in HIV-1-Infected Individuals
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): rilpivirine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of rilpivirine in people with HIV Infections as compared to allele T.
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: rs869312146
Drug(s): migalastat
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is associated with increased response to migalastat in people with Fabry Disease.
Notes: Patients carrying the T 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 Met187Ile in the paper.
Article: Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children
Gene: CYP2B6
Variant/haplotype: CYP2B6*6
Drug(s): methadone
Phenotype category: Toxicity
Significant: not stated
Association: CYP2B6 *6/*6 is associated with decreased metabolism of methadone in children with Pain, Postoperative and Scoliosis.
Notes: prospective study of methadone in children undergoing major surgery. "CYP2B6 poor metabolizers (*6/*6) had >twofold lower R- and S-methadone metabolites to methadone ratio compared with normal and rapid metabolizers in adolescents who received multiple doses of methadone intraoperatively and postoperatively. "
Article: The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with decreased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: Alleles complemented to plus chromosomal strand. There were no *1/*1 (TT) observed. " There was a significant difference when C/D ratios of homozygote CYP3A5 *3/*3 carriers were compared between 2 and 8 weeks"
Article: Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy
Gene: ATP5F1E
Variant/haplotype: rs1059150
Drug(s): adalimumab, certolizumab pegol, etanercept, glucocorticoids, infliximab, methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to adalimumab, certolizumab pegol, etanercept, glucocorticoids, infliximab or methotrexate in women with Arthritis, Rheumatoid as compared to genotype TT.
Notes: Response measured after 12 weeks of treatment. Alleles described as HLA-E *01:01 and *01:03.
Article: CYP2C19*17 association with higher plasma 4-hydroxy tamoxifen in Pakistani (estrogen-positive) breast cancer patients
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): 4-hydroxytamoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*17 + *17/*17 is associated with increased concentrations of 4-hydroxytamoxifen in people with Breast Neoplasms as compared to CYP2C19 *1/*1.
Notes: "For the CYP2C19*17 locus, the median total metabolic ratio of 4-OH-Tam (TMR-4-OH-Tam) was significantly higher in the heterozygous (187.91) (P < 0.001) and mutant (210.90) (P < 0.001) genotypes, compared to the wild-type (122.46) genotypes (Table 4 and Figure 6(A))."
Article: An Investigational Study on the Role of CYP2D6, CYP3A4 and UGTs Genetic Variation on Fesoterodine Pharmacokinetics in Young Healthy Volunteers
Gene: CYP3A4
Variant/haplotype: CYP3A4 intermediate metabolizer
Drug(s): fesoterodine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A4 intermediate metabolizer is associated with increased clearance of fesoterodine in healthy individuals as compared to CYP3A4 normal metabolizer.
Notes: "The CYP3A4 IMs showed a lower AUC/DW (puv = 0.046; β = −0.272, R2 =0.410, pmv = 0.047) and higher CL/F (puv = 0.044; β = 0.275, R2 =0.409, pmv = 0.045) than the NMs (Table 3)." The 10 SNPs for CYP3A4 measured are listed in table 5.
Article: The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool
Gene: SLC2A9
Variant/haplotype: rs11942223
Drug(s): allopurinol
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of allopurinol in people with Gout as compared to allele C.
Article: Relationship of CYP3A5 genotype and ABCB1 diplotype to tacrolimus disposition in Brazilian kidney transplant patients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with increased dose of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: 3 to 12 months post-transplant. Using chi-squared analysis.
Article: Role of IL6R Genetic Variants in Predicting Response to Tocilizumab in Patients with Rheumatoid Arthritis
Gene: IL6R
Variant/haplotype: rs4845625
Drug(s): tocilizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with increased response to tocilizumab in people with Arthritis, Rheumatoid as compared to genotype CC.
Notes: Response measured using Disease activity score including 28 joints (DAS28), a satisfactory European League Against Rheumatism (EULAR) response, and low disease activity (LDA) achievement.
Article: Associations of OPRM1 A118G and Alcohol Sensitivity with Intravenous Alcohol Self-Administration in Young Adults
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AG + GG is associated with increased concentrations of ethanol in healthy individuals as compared to genotype AA.
Notes: Individuals with the AG or GG genotype achieved significantly higher mean peak breath alcohol concentration as compared to those with the AA genotype. Those with the AG or GG genotype also showed significantly more post-priming drink requests compared to those with the AA genotype. Genotype accounted for 8% of the variance in peak breath alcohol concentration. Participants self-administered alcohol intravenously (6% ethanol solution) over a period of 2 hours.
Article: Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele T.
Notes: There was no significant association between this variant and cessation of opioid use.
Article: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor, tezacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype del/del is associated with response to ivacaftor and tezacaftor in people with Cystic Fibrosis.
Notes: F508del allele. Study has multiple phases - a tezacaftor dose escalation phase and an efficacy testing phase using 100mg tezacaftor and 150mg ivacaftor. Significant improvements in sweat chloride level, ppFEV1 and CFQ-R scores were observed in the dose escalation phase however only sweat chloride levels showed a significant improvement in the efficacy testing phase.
Article: CYP3A4*1B and CYP3A5*3 SNPs significantly impact the response of Egyptian candidates to high-intensity statin therapy to atorvastatin
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of atorvastatin in people with Cardiovascular Disease or Hyperlipidemias as compared to genotypes CC + CT.
Notes: "Atorvastatin plasma levels (in ng/ml) were greater in carriers of the T/T genotype than in carriers of the other genotypes (C/T) and (C/C) (P value < 0.05). The plasma levels were 7.59 ± 2.69 for the T/T genotype and 3.39 ± 1.03 and 3.08 ± 0.82 for the C/T and C/C genotypes, respectively (Table 5)."
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: ANKK1
Variant/haplotype: rs1800497
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele G.
Notes: Methadone maintenance dose was not associated with genotype of the SNP but it was correlated to the highest dose ever used. Multiple doses versus single dose, body weight, history of cocaine dependence and ethnicity (Asian>Caucasian>African) were independently associated with methadone dose in multiple regression analysis.
Article: Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of warfarin as compared to genotype CC.
Notes: In this meta-analysis of warfarin Dose in Black-African Patients, this variant is associated with 18.1mg/week less warfarin dose requirement compared to wild-type homozygotes.