shlokn/autogkb huggingface dataset:
Article: Sub‐ and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study
Gene: CYP2B6
Variant/haplotype: CYP2B6 intermediate metabolizer
Drug(s): efavirenz
Phenotype category: Efficacy
Significant: no
Association: CYP2B6 normal metabolizer and intermediate metabolizer is associated with increased resistance to efavirenz in children with HIV infectious disease as compared to CYP2B6 poor metabolizer.
Notes: "extensive metabolizer (EM), 516GGj983TT, intermediate metabolizer (IM), 516GGj983TC or 516GTj983TT, slow metabolizer (SM) 516GTj983TC or 516TTj983TT. "HIV drug resistance at baseline, viraemia and acquisition of new HIV drug-resistant mutations at Week 24 were all more frequent among EM and IM compared to SM (n.s.) (Table S2)."
Article: The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer genotype
Drug(s): oxymorphone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 poor metabolizer is associated with decreased exposure to oxymorphone in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: The AUC for oxymorphone was significantly lower in poor metabolizers than in extensive metabolizers.
Article: Association Between Vitamin D Receptor Polymorphism and the Response to Helicobacter Pylori Treatment
Gene: VDR
Variant/haplotype: rs2228570
Drug(s): amoxicillin, clarithromycin, omeprazole
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to amoxicillin, clarithromycin and omeprazole in people with Helicobacter Infections as compared to allele G.
Notes: Alleles complemented to plus chromosomal strand.
Article: Genome-wide association study of patient and clinician rated global impression severity during antipsychotic treatment
Variant/haplotype: rs8050896
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to risperidone in people with Schizophrenia as compared to allele A.
Notes: The number of T alleles present in a patient was negatively associated with CGI-S score.
Article: Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CT is associated with increased clearance of tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: Patients with the CT genotype had 26% higher clearance (p=0.08) and 37% lower bioavailability (no p-value given) as compared to those with the CC genotype. The primary aim of the present analysis was to develop a nonparametric population pharmacokinetic model for future use for tacrolimus dosing in a clinical prospective setting in renal transplant recipients. Initially, knowledge of each patient's CYP3A5 genotype improves the predictions, but after obtaining three to four Tac trough concentrations, the model does at least as well without the CYP3A5 genotype information.
Article: GENOME-WIDE AND GENE-BASED META-ANALYSES IDENTIFY NOVEL LOCI INFLUENCING BLOOD PRESSURE RESPONSE TO HYDROCHLOROTHIAZIDE
Gene: HSD3B1
Variant/haplotype: rs7553527
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to hydrochlorothiazide in people with Hypertension as compared to genotype TT.
Notes: Participants were from GENRES study, GERA-1 study, HCTZ-Milan study, NORDIL study, PEAR-1 study, PHSS study.
Article: No Evidence That G6PD Deficiency Affects the Efficacy or Safety of Daunorubicin in Acute Lymphoblastic Leukemia Induction Therapy
Gene: G6PD
Variant/haplotype: G6PD deficiency
Drug(s): daunorubicin
Phenotype category: Efficacy
Significant: no
Association: G6PD deficiency is not associated with response to daunorubicin in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma.
Notes: No significant association between G6PD deficient genotypes and the number of patients who achieve minimal residual disease (MRD) >1% following daunorubicin treatment.
Article: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A4
Variant/haplotype: rs67666821
Drug(s): ambrisentan, aripiprazole, atorvastatin, donepezil, olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of ambrisentan, aripiprazole, atorvastatin, donepezil or olanzapine in healthy individuals as compared to allele del.
Notes: No significant changes in PK parameters in the presence of the T allele. The T allele is also referred to in the paper as the CYP3A4*20 allele.
Article: Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): phenprocoumon
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with increased dose of phenprocoumon as compared to genotypes CT + TT.
Notes: Daily dose of phenprocoumon is significantly associated with rs9923231 genotype in a gene dose effect: GG>AG>AA. Daily dose is also negatively correlated with age. This study published an algorithm for daily dose that includes height, although height was not significant in univariate analysis. This SNP is also significantly associated with phenprocoumon concentration in the same gene-dose effect (GG>AG>AA).
Article: Factors associated with fluoxetine and norfluoxetine plasma concentrations and clinical response in Mexican patients with mental disorders
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*4, CYP2D6*10
Drug(s): fluoxetine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *1/*1 + *10/*10 + *1/*4 + *1/*10 (assigned as normal metabolizer phenotype) is associated with decreased concentrations of fluoxetine in people with Anxiety Disorders, Depression or Depressive Disorder, Major as compared to CYP2D6 *10/*4 (assigned as intermediate metabolizer phenotype) .
Notes: For CYP2D6 phenotypes were assigned as CYP2D6 extensive (*1/*1, *10/*10, *1/*4, *1/*10), intermediate (*10/*4) and poor; (*4/*4) metabolizers using CYP2D6*4 (rs3892097), and CYP2D6*10 (rs1065852). Also, CYP2D6 extensive metabolizers had almost twice; the value of norfluoxetine/fluoxetine ratios (0.9 (0.7–1.7)) than; patients with CYP2D6 intermediate metabolism (0.5 (0.3–0.8))
Article: Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms
Gene: IFNL3
Variant/haplotype: rs8099917
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C as compared to genotypes GG + GT.
Notes: Though this SNP is not directly linked to response, it is associated with significantly lower baseline plasma levels of IP-10. Lower levels of IP-10 were found to be statistically significantly associated with better treatment outcome. This SNP was found to be in strong linkage disequilibrium with rs12979860.
Article: Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition
Gene: SLCO1B1
Variant/haplotype: SLCO1B1*1, SLCO1B1*5, SLCO1B1*37
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: SLCO1B1 *5 is associated with decreased clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to SLCO1B1 *1 + *37.
Notes: Please note *1B was mentioned in the article. SLCO1B1*1B was consolidated into  SLCO1B1*37  by PharmVar in 2021.
Article: Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
Gene: GABRA1
Variant/haplotype: rs2279020
Drug(s): propofol
Phenotype category: Other
Significant: yes
Association: Genotype GG is associated with increased response to propofol as compared to genotypes AA + AG.
Notes: The GG (57.15±13.29) genotype was associated with lower BIS values as compared with the AA and AG genotypes vs. (61.43±10.51) indicating increased susceptibility to propofol in GG genotype. Please note: the authors examined 58 SNPs but did not do multiple testing corrections.; However, the GG genotype was also associated with a smaller decrease in mean arterial pressure (MAP) after propofol as compared to the AG+ AA genotypes (-9.44% vs. -12.16%). Please note: the authors examined 58 SNPs but did not do multiple testing corrections.
Article: Identification of novel CYP2A6*1B variants; the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*46 is associated with increased clearance of nicotine as compared to CYP2A6 *1/*1.
Notes: Includes alleles *1B1-*1B15. Please note that the *46 allele is described as the *1B1 allele in the paper and has subsequently been reassigned by PharmVar.
Article: The Association between ABCG2 421C>A (rs2231142) Polymorphism and Rosuvastatin Pharmacokinetics: A Systematic Review and Meta-Analysis
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): rosuvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT is associated with increased concentrations of rosuvastatin as compared to genotype GG.
Notes: Alleles complemented to plus chromosomal strand. Meta-analysis of 8 studies looking at AUC and Cmax of rosuvastatin.
Article: Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis
Gene: GGH
Variant/haplotype: rs11545078
Drug(s): methotrexate
Phenotype category: Toxicity
Significant: yes
Association: Genotypes AA + AG is associated with increased discontinuation of methotrexate in people with Arthritis, Rheumatoid as compared to genotype GG.
Notes: Patients receiving MTX and bDMARD treatment (combined treatment) at the time of the study were considered “tolerant” to MTX. Patients receiving bDMARD monotherapy at the study visit were asked about the reason for MTX discontinuation. In cases of discontinuation due to adverse events or toxicity (such as nausea; vomiting; dyspepsia; alopecia; oral ulcers; leukopenia; hepatic alterations, defined as alanine aminotransferase levels greater than 1.5 times the upper normal limit; or pulmonary toxicity), these patients were considered “intolerant” to MTX.
Article: Relationship between Genotypes Sult1a2 and Cyp2d6 and Tamoxifen Metabolism in Breast Cancer Patients
Gene: SULT1A2
Variant/haplotype: rs1136703
Drug(s): 4-hydroxytamoxifen, endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA are associated with decreased concentrations of 4-hydroxytamoxifen or endoxifen in women with Breast Neoplasms as compared to genotypes AG + GG.
Notes: as part of haplotype *1*1 vs *1/*2 + *2/*2 (rs1136703A>G and rs1059491T>G). Pre and postmenopausal woman with estrogen receptor-positive breast cancer undergoing tam treatment after surgery and chemotherapy/radiation. Patients were excluded if tamoxifen therapy was started with either chemotherapy or radiation.
Article: The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*5, CYP2D6*10, CYP2D6*21
Drug(s): aripiprazole
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *1/*1 + *1/*10 + *1/*21 + *1/*5 (assigned as normal metabolizer phenotype) are not associated with decreased metabolism of aripiprazole in healthy individuals also being given fluvoxamine as compared to CYP2D6 *10/*10 + *5/*10 (assigned as intermediate metabolizer phenotype) .
Notes: The coadministration of fluvoxamine did not cause a large difference in aripiprazole metabolism in extensive metabolizers as compared to intermediate metabolizers.
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: ABCB1
Variant/haplotype: rs10248420
Drug(s): clozapine
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased clinical benefit to clozapine in people with Schizophrenia or Psychotic Disorder as compared to allele A.
Notes: Alleles complemented. Table does not state which allele or direction of effect for these SNPs, so assuming minor allele and benefit, PANSS beta is in Table negative. "four SNPs in two genes were significantly associated with the total PANSS score: rs7787082 and rs10248420 in ABCB1 and rs2133251840 and rs762502 in DRD4 (Table 5). Among these, only one SNP in DRD4 (rs2133251840) resulted in different total PANSS scores at visits 3 and 4 according to its genotype"
Article: ADRB2 Gene Polymorphisms and Salbutamol Responsiveness in Serbian Children with Asthma
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): salmeterol
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to salmeterol in children Asthma as compared to allele A.
Notes: The presence of the G allele in the ADRB2 variant +46A>G correlates with better bronchodilator response to salbutamol.
Article: Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real‐life clinical practice
Gene: TNFAIP3
Variant/haplotype: rs610604
Drug(s): tildrakizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased clinical benefit to tildrakizumab in people with Psoriasis as compared to genotypes GT + TT.
Notes: "Our data also suggest that patients carrying the genotype GG for rs610604 (TNFAIP3), CTGT/− for rs72167053 (PDE4D) and CT for rs9373839 (ATG5) had a higher probability to not achieve PASI ≤1 after 12 months of tildrakizumab treatment, while those with CT for rs708567 (IL17RC) have a higher chance to have an optimal response to this treatment."
Article: Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A4 *22 is not associated with increased exposure to tacrolimus in people with Kidney Transplantation as compared to CYP3A4 *1/*1.
Notes: "For the CYP3A4*22 allele, the C0/D ratio did not differ significantly between non-carriers and carriers (p = 0.413)."
Article: Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): rabeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *2 + *3 are not associated with response to rabeprazole in people with Ulcer as compared to CYP2C19 *1.
Notes: In patients with large artificial gastric ulcers after endoscopic submucosal dissection due to gastric adenoma or early gastric cancers. The S stage rates at 4 and 8 weeks were similar in the rabeprazole only or rabeprazole plus rebamipide, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype.
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: SLC19A1
Variant/haplotype: rs3788200
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.
Article: Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*10
Drug(s): N-desmethyltamoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *10/*10 + *1/*10 is associated with increased concentrations of n-desmethyltamoxifen in women with Breast Neoplasms as compared to CYP2D6 *1/*1.
Notes: The association was not significant but a stepwise decrease in median 4-hydroxytamoxifen concentration was observed when comparing patients with zero, one or two copies of the CYP2D6*10 allele. Patients (pre- (83%) and postmenopausal (17%)) with ER and/or PR positive breast tumors, which received 20 mg tamoxifen daily. Patients taking CYP2D6 inhibitors were excluded. DNA extracted from blood and screened for the following: *2 (2850C>T; rs16947), *2A (–1584C>G), *3 (2549delA; rs35742686), *4 (1846G>A; rs3892097), *5 (CYP2D6del), *6 (1707delT; rs5030655), *7 (2935A>C; rs5030867), *8 (1758G>T), *9 (2615-2617delAAG; rs5030656), *10 (100C>T; rs1065852), *12 (124G>A; rs5030862), *14 (1758G>A), *17 (1023C>T; rs28371706), *29 (1659G>A; rs61736512), *41 (2988G>A; rs28371725) and *xN (dup). [pre-menopausal][post-menopausal] [adjuvant] [DNA source: blood]
Article: Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD
Gene: ADGRL3
Variant/haplotype: rs1947274
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele C.
Article: Population Pharmacokinetics and Pharmacogenetics Analysis of Rilpivirine in HIV-1-Infected Individuals
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): rilpivirine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of rilpivirine in people with HIV Infections as compared to allele G.
Article: Impact of Pharmacogenetic Markers of CYP2B6, Clinical Factors, and Drug-Drug Interaction on Efavirenz Concentrations in HIV/Tuberculosis-Coinfected Patients
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GT is associated with decreased clearance of efavirenz in people with HIV Infections as compared to genotype GG.
Notes: As shown by increased plasma concentrations (units = mg/L) for those with the GT genotype compared to those with the GG genotype. Fasting plasma efavirenz concentrations were measured 12 hours after the last dose, and after 12 weeks of treatment.
Article: Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment
Variant/haplotype: low activity
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A low activity is associated with increased trough concentration of methadone as compared to CYP3A high activity.
Notes: CYP3A phenotyping carried out using midazolam.
Article: GENETIC VARIATION IN CYP4A11 AND BLOOD PRESSURE RESPONSE TO MINERALOCORTICOID RECEPTOR ANTAGONISM OR ENAC INHIBITION: AN EXPLORATORY PILOT STUDY IN AFRICAN AMERICANS
Gene: CYP4A11
Variant/haplotype: rs3890011
Drug(s): spironolactone
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to spironolactone in people with Hypertension as compared to genotypes CG + GG.
Notes: This variant was in complete disequilibrium with rs1126742. Alleles are reported as described in the paper however, because this is a G/C SNP, users should be aware that there is ambiguity as to whether the alleles are reported as on the positive strand. Patients with the CC genotype and receiving spironolactone monotherapy did not have a reduction in systolic or diastolic blood pressure while those with the CG or GG genotypes did.
Article: The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of warfarin in people with Atrial Fibrillation, heart valve replacement, Hypertension, Pulmonary, Pulmonary Embolism or Venous Thrombosis as compared to genotype CC.
Notes: Please note: alleles have been complemented to the + strand.
Article: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
Gene: CHST3
Variant/haplotype: rs12418
Drug(s): docetaxel, thalidomide
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to docetaxel and thalidomide in people with Prostatic Neoplasms as compared to allele G.
Notes: (allele inferred by frequency comparison with dbSNP, actual base not listed in paper)
Article: Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study
Gene: CYP2B6
Variant/haplotype: rs2279343
Drug(s): (S)-methadone
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele G is associated with decreased clearance of (S)-methadone in people with HIV Infections as compared to allele A.
Notes: "The CYP 2B6*4 variant decreased S-methadone CL/F by 18%. "
Article: Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): everolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with increased concentrations of everolimus in women with Breast Neoplasms as compared to genotype GG.
Notes: The AG allele was associated with 2.7-fold higher everolimus concentrations compared to the GG genotype. There were no individuals with the AA genotype. Please note: alleles have been complemented to the positive chromosomal strand.
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: rs104894828
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 Arg301Gln in the paper.
Article: Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi‐physiologic population pharmacokinetic approach
Gene: SLC22A1
Variant/haplotype: rs2282143
Drug(s): proguanil
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype CT is associated with increased exposure to proguanil in healthy individuals as compared to genotype CC.
Notes: "The CT genotype showed a 1.2‐fold higher systemic exposure of proguanil and a 0.6‐fold lower exposure of cycloguanil compared to those in subjects with the CC genotype, resulting in a 0.5 to 0.6‐fold lower metabolic ratio. "