shlokn/autogkb huggingface dataset:
Article: Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer phenotype
Drug(s): ethylmorphine
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 poor metabolizer is associated with decreased metabolism of ethylmorphine in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: Study of ethylmorphine metabolism in ten healthy volunteers. Authors genotyped for the CYP2D6*3, *4, *5 and *9 alleles, referred to in the paper as CYP2D6A, CYP2D6B, CYP2D6D and CYP2D6C respectively. One subject had the *1/*3 genotype, two were *1/*4 and two had the *1/*5 genotype. All other subjects were *1/*1. However, the authors describe their results in terms of the metabolizer phenotypes obtained using ethylmorphine as a probe drug, which identified two poor metabolizers (one *1/*3 and one *1/*5) and eight normal metabolizers. The discussion section of the paper mentions that ethylmorphine is not a suitable probe drug for determining CYP2D6 activity, due to the existence of other ethylmorphine metabolic pathways via UGT1A and CYP3A.
Article: Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotypes CT + TT is not associated with response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotype CC.
Notes: This genotype was not significantly with associated with likelihood of achieving major molecular response (MMR) within 12 months. MMR was classified based on BCR-ABL to control gene transcript ratios, expressed on the International Scale; MMR was a ratio <= 0.1%. Please note that alleles have been complemented to the plus chromosomal strand.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs10954808
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: Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation
Gene: CTH
Variant/haplotype: rs1021737
Drug(s): busulfan
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with clearance of busulfan in children with Hematopoietic stem cell transplantation as compared to genotypes GG + GT.
Article: Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria
Gene: CR1
Variant/haplotype: rs3811381
Drug(s): eculizumab
Phenotype category: Efficacy
Significant: no
Association: Genotypes CG + GG is not associated with response to eculizumab in people with paroxysmal nocturnal hemoglobinuria as compared to genotype CC.
Notes: Response was defined as no red blood cell transfusion at any time after the first 6 months on eculizumab treatment (patients had a median follow-up of 52 months, range of 11-98 months). In the paper, CC = Pro/Pro.
Article: Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis
Gene: CYP3A5
Variant/haplotype: CYP3A5 poor metabolizer
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 poor metabolizer is associated with increased concentrations of carbamazepine as compared to CYP3A5 normal metabolizer and intermediate metabolizer.
Notes: "CYP3A5 poor metabolizers exhibited a 12% (95% CI, 3%-22%) plasma concentration increase compared with carriers of functional CYP3A5 haplotypes (Table 3)." "CYP3A5*3: rs776746"
Article: A case report of voriconazole therapy failure in a homozygous ultrarapid CYP2C19*17/*17 patient comedicated with carbamazepine
Gene: CYP2C19
Variant/haplotype: CYP2C19*17
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C19 *17/*17 (assigned as ultrarapid metabolizer phenotype) is associated with decreased concentrations of voriconazole.
Notes: Case report: Patient had undetectable plasma levels of the drug, resulting in decreased exposure and discontinuation of drug (switched to alternative drug). Patient also taking carbamazepine.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Variant/haplotype: rs3008604
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of vancomycin as compared to allele C.
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: Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): clopidogrel thiol metabolite H4
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with exposure to clopidogrel thiol metabolite H4 as compared to allele G.
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: 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: rs398123226
Drug(s): migalastat
Phenotype category: Efficacy
Significant: not stated
Association: Allele C is associated with increased response to migalastat in people with Fabry Disease.
Notes: Patients carrying the C 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 Asp322Glu in the paper.
Article: Variants Identified in a GWAS Meta-Analysis for Blood Lipids Are Associated with the Lipid Response to Fenofibrate
Gene: APOA1
Variant/haplotype: rs964184
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to fenofibrate in people with Hypertriglyceridemia as compared to allele C.
Notes: Patients with the G allele had a greater increase in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) level between baseline and either 3 weeks or 8 weeks of fenofibrate treatment, as compared to those with the C allele. Two cohorts were used: the discovery cohort came from the National Heart, Lung and Blood Institute GOLDN study population, and the replication cohort came from the Pharmacogenetics of Hypertriglyceridemia in Hispanics (HyperTG) study. Participants from the GOLDN study received fenofibrate treatment for 3 weeks, participants from HyperTG received it for 8 weeks. Differences in the discovery study population were significant after correction for multiple testing.
Article: SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased response to hmg coa reductase inhibitors in people with Cardiovascular Diseases as compared to allele T.
Notes: as measured by plasma LDL-c.
Article: CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): pantoprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 is associated with decreased clearance of pantoprazole in healthy individuals as compared to CYP2C19 *1/*1.
Notes: AG = *1/*2 and GG = *1/*1. The study was done using pantoprazole. *2/*17 (n = 6) had concentration-time curves similar to *1/*1 subjects (typed only for *2 and *17).
Article: Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states1
Gene: APOA5
Variant/haplotype: rs662799
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: not stated
Association: Genotypes AG + GG are associated with increased response to fenofibrate in people with Hypertriglyceridemia.
Notes: When combined with rs780094 CT + TT 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. Please note alleles have been complemented to the plus chromosomal strand.
Article: Effects of OPRM1 and ABCB1 gene polymorphisms on the analgesic effect and dose of sufentanil after thoracoscopic-assisted radical resection of lung cancer
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): sufentanil
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AC are associated with increased dose of sufentanil in people with Lung Neoplasms and Pain, Postoperative as compared to genotype CC.
Notes: Patients with the AA genotype had significantly increased sufentanil consumption compared to patients with the AC or CC genotypes, while those with the AC genotype had significantly increased compared to patients with the CC genotype. Please note that alleles have been complemented to the positive strand.
Article: A Single Site Population Study to Investigate CYP2D6 Phenotype of Patients with Persistent Non-Malignant Pain
Gene: CYP2D6
Variant/haplotype: CYP2D6 normal metabolizers
Drug(s): codeine
Phenotype category: Efficacy
Significant: not stated
Association: CYP2D6 normal metabolizer is associated with increased response to codeine in people with Pain as compared to CYP2D6 ultrarapid metabolizer.
Notes: All CYP2D6 PMs, IMs and UMs in the study cohort were categorized as non-responders to codeine. Patients were genotyped for the *1, *2, *3, *4, *5, *6, *9, *10, *41 alleles as well as for allele duplication. Note that patients with a CYP2D6 activity score of 1 were assigned as normal metabolizers.
Article: Variation in Mu-Opioid Receptor Gene (OPRM1) as a Moderator of Naltrexone Treatment to Reduce Heavy Drinking in a High Functioning Cohort
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to naltrexone in men with Alcoholism as compared to allele A.
Notes: A significant association was seen between the G allele and the likelihood of achieving a level of non-hazardous drinking (defined as drinking less than 14 standard drinks and having nor heavy drinking days in one week).; However, no significant main effect was observed between rs1799971, naltrexone and either the weekly sum of standard drinks or the number of heavy drinking days.
Article: Serotonin transporter 5-HTTLPR polymorphism and escitalopram treatment response in patients with major depressive disorder
Gene: BDNF
Variant/haplotype: rs962369
Drug(s): escitalopram
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with decreased response to escitalopram in people with Major Depressive Disorder as compared to allele T (assigned as normal metabolizer phenotype) .
Notes: "No significant relationship between HTR2A rs9316233 and BDNF rs962369 variants with response to escitalopram treatment was observed." Table 3 lists C as minor allele and T as common allele.
Article: Pharmacogenetic guidance: individualized medicine promotes enhanced pain outcomes
Gene: MTHFR
Variant/haplotype: rs1801133
Drug(s): folic acid
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele A is associated with decreased metabolism of folic acid.
Notes: Please note that alleles have been complemented to the positive stand.; Case study of a patient with the A allele at rs1801133 and the G allele at rs1801131 who subsequently responded to folate supplementation.
Article: Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of pazopanib
Gene: KDR
Variant/haplotype: rs34231037
Drug(s): pazopanib
Phenotype category: Efficacy
Significant: yes
Association: Genotype AG is associated with increased response to pazopanib in people with Carcinoma, Renal Cell as compared to genotype AA.
Notes: Patients with the G allele had greater decline over 4 weeks in [sVEGFR2] with; pazopanib exposure compared to non-carriers (mean decrease -3.5ng/mL vs -2.3 ng/mL, they also had lower baseline [sVEGFR2] measures. Serum VEGFR2 concentrations [sVEGFR2] is a pharmacodynamic biomarker for VEGFR2 inhibitors. No GG homozygotes were shown.
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: CHRNB4
Variant/haplotype: rs7178270
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele G is not associated with exposure to nicotine in men as compared to allele C.
Notes: No significant association between this allele and status as a smoker or non-smoker.
Article: Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies
Gene: CHRNB2
Variant/haplotype: rs2072661
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bupropion, nicotine and varenicline in people with Tobacco Use Disorder as compared to allele G.
Notes: Authors looked at the effect of variants on response to the smoking cessation therapies varenicline, bupropion and nicotine replacement therapy.; Please note that alleles have been complemented to the positive strand.
Article: Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes
Gene: EPHX1
Variant/haplotype: EPHX1 poor metabolizer
Drug(s): acetylcysteine
Phenotype category: Efficacy
Significant: yes
Association: EPHX1 poor metabolizer is associated with increased response to acetylcysteine in people with Pulmonary Disease, Chronic Obstructive as compared to genotype fast/normal (assigned as intermediate metabolizer and normal metabolizer phenotype) .
Notes: Efficacy measured as improvement in FEV1, FEV1 % predicted, and SGRQ symptom score. Efficacy also measured in terms of reduction of exacerbation rate.
Article: Cytochrome P450 (CYP2C9*2,*3) & vitamin-K epoxide reductase complex (VKORC1 -1639G<A) gene polymorphisms & their effect on acenocoumarol dose in patients with mechanical heart valve replacement
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): acenocoumarol
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of acenocoumarol as compared to allele C.
Notes: The CYP2C9*2, *3 and VKORC1 rs9923231 are analyzed together. Patients carrying any of the variant alleles was 34% among those receiving a low dose of =20 mg/wk while it was 13.8 per cent in those receiving >20 mg/wk (P=0.014).
Article: Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma
Gene: C6
Variant/haplotype: rs9200
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CC + CT are not associated with dose-adjusted trough concentrations of tacrolimus in people with liver transplantation as compared to genotype TT.
Notes: When considering DONOR genotype - no significant difference in concentration/dose ratio was seen between those with the CC or CT genotype and to those with the TT genotype at weeks 1-4 of treatment. Patients with hepatocellular carcinoma. Please note that alleles have been complemented to the plus chromosomal strand.
Article: IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients
Gene: CTLA4
Variant/haplotype: rs4553808
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AG + GG is associated with increased exposure to tacrolimus in people with Kidney Transplantation as compared to genotype AA.
Notes: This association was significant in CYP3A5 nonexpressors but the opposite association was seen in CYP3A5 expressers. The time of measurement was 30 days after transplantation. Day 7 and day 90 after transplantation did not show a significant association.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: CYP2B6
Variant/haplotype: rs2279343
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: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs866325353
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 T.
Notes: Significance threshold was set at 5.0E-9.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Variant/haplotype: rs2859229
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele T.
Article: Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Variant/haplotype: rs7624766
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele A.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: LRIG3
Variant/haplotype: rs7970054
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of tenofovir in people with HIV Infections as compared to allele T.
Notes: Significance threshold was set at 6.0E-7.
Article: Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking
Gene: CHRNA5
Variant/haplotype: rs16969968
Drug(s): nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to nicotine or varenicline in people with Tobacco Use Disorder as compared to genotypes AA + AG.
Notes: Response here refers to smoking cessation outcomes at 7 days and nicotine refers to nicotine patches. Smoking cessation outcomes at 6 months and 12 months were also not significantly associated with genotype.
Article: Genome-wide study of methotrexate clearance replicates SLCO1B1
Gene: SLCO1B1
Variant/haplotype: rs11045821
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: Effect of UGT2B10, UGT2B17, FMO3, and OCT2 Genetic Variation on Nicotine and Cotinine Pharmacokinetics and Smoking in African Americans
Gene: UGT2B10
Variant/haplotype: rs2942857
Drug(s): cotinine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with decreased clearance of cotinine in people with Tobacco Use Disorder as compared to genotypes AA + AC.
Notes: This annotation was on rs116294140, but dbSNP has merged these two rs IDs.
Article: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele A.
Notes: Please note: alleles have been complemented to the + chromosomal strand.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs112914324
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 G.
Notes: Significance threshold was set at 5.0E-9.
Article: Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations
Gene: NRG1
Variant/haplotype: rs17716295
Drug(s): antipsychotics
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to antipsychotics in people with Schizophrenia as compared to allele C.
Notes: In high severity schizophrenia patient subgroup
Article: Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder
Gene: PER3
Variant/haplotype: rs2640909
Drug(s): lithium
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with increased response to lithium in people with Bipolar Disorder as compared to allele T.
Article: ERICH3: vesicular association and antidepressant treatment response
Gene: ERICH3
Variant/haplotype: rs11580409
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to antidepressants as compared to allele A.
Notes: Meta-analysis combined samples from four independent antidepressant studies, STAR*D, ISPC, PReDICT and PGRN-AMPS. Treatment “response” was defined as a reduction of at least 50% in depression score as determined by use of the 17-item Hamilton Depression Rating Scale or the 16-item Quick Inventory of Depressive Symptomatology.; rating scale.