shlokn/autogkb huggingface dataset:
Article: Germline Polymorphisms as Biomarkers of Tumor Response in Colorectal Cancer Patients Treated with Anti-EGFR Monoclonal Antibodies: A Systematic Review and Meta-Analysis
Gene: EGFR
Variant/haplotype: rs712829
Drug(s): cetuximab, panitumumab
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to cetuximab or panitumumab in people with Colorectal Neoplasms as compared to allele G.
Notes: Meta-analysis with 3 studies. The authors did not provide the exact number of patients but stated that "the median number of patients per analysis was 110 (range 50 - 740)". Most definitions of response were variations of the RECIST criteria.
Article: Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): sertraline
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2/*2 + *2/*3 (assigned as poor metabolizer phenotype) are associated with decreased metabolism of sertraline as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: The harmonized sertraline serum concentrations in CYP2C19 PMs (carriers of 2 no function alleles) was 2.68-fold (p < 0.001, 95% confidence interval [CI] 2.16–3.31) higher compared to CYP2C19 NMs (*1/*1). A 3.00-fold (p < 0.001, 95% CI 2.46–3.66) higher concentration of N-desmethylsertraline was found in PMs compared to NMs. Compared with NMs, the N-desmethylsertraline-to-sertraline metabolic ratio was 1.26-fold higher in PMs (p = 0.009, 95% CI 1.07–1.46). In CYP2C19 PMs, the OR for having one or more TDM measurements above the target concentration range of 250 nM was 8.69 (p < 0.001, 95% CI 3.88–19.19). The study detected *2, *3, and *4 as no function alleles but did not report specific diplotypes. The diplotypes used in the annotations are representative.
Article: Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*17
Drug(s): metronidazole
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2A6 *17 is not associated with clearance of metronidazole in infants as compared to CYP2A6 *1.
Notes: Infants with the *1/*17 genotype had similar metronidazole clearance and metabolic ratio values as *1/*1 infants.
Article: Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): nevirapine
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Genotype CC is associated with increased clearance of nevirapine in people with HIV Infections as compared to genotypes CT + TT.
Notes: The CYP3A5*3 allele (rs776746 allele C) significantly decreases area under the concentration time curve (AUC) in a multiple variable model for determining nevirapine AUC, also including rs3745274 allele T and age. [stat_test: multiple linear regression]
Article: Underlying genetic structure impacts the association between CYP2B6 polymorphisms and response to efavirenz and nevirapine
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz, non-nucleoside reverse transcriptase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to efavirenz or non-nucleoside reverse transcriptase inhibitors in women with HIV Infections as compared to genotype GG.
Notes: This variant was significantly associated with virologic suppression (OR=3.61, 95% CI 1.16-11.22, p trend=0.03) after adjustment for genetic ancestry PCs.
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs31244
Drug(s): quetiapine
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to quetiapine in people with Schizophrenia as compared to genotypes AA + AG.
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: Thymidylate Synthase Genotype-Directed Neoadjuvant Chemoradiation for Patients With Rectal Adenocarcinoma
Gene: C18orf56, TYMS
Variant/haplotype: rs45445694
Drug(s): irinotecan
Phenotype category: Dosage
Significant: no
Association: Genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)3/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)4 is associated with increased dose of irinotecan in people with Rectal Neoplasms as compared to genotypes (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)2 + (CCGCGCCACTTGGCCTGCCTCCGTCCCG)2/(CCGCGCCACTTGGCCTGCCTCCGTCCCG)3.
Notes: Patients with TYMS *2/*2, *2/*3, or *2/*4 (good risk) were treated with standard chemoradiotherapy using infusional FU at 225 mg/m(2)/d. Patients with TYMS *3/*3 or *3/*4 (poor risk) were treated with FU/RT plus weekly intravenous irinotecan at 50 mg/m(2).
Article: Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations
Gene: CCL2
Variant/haplotype: rs4795893
Drug(s): antipsychotics
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to antipsychotics in people with Schizophrenia as compared to allele A.
Notes: In low severity schizophrenia patient subgroup
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs142693425
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele CTT is not associated with clearance of tenofovir in people with HIV Infections as compared to allele del.
Notes: Significance threshold was set at 5.0E-9.
Article: Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotypes AA + AG.
Notes: This genotype was not significantly with associated with likelihood of achieving complete molecular response (CMR) within 12 months. CMR was classified based on BCR-ABL to control gene transcript ratios, expressed on the International Scale; CMR was a ratio <= 0.0032%. Please note that alleles have been complemented to the plus chromosomal strand, and that this SNP was listed as rs60023214.
Article: Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): pravastatin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with response to pravastatin in children with Hyperlipoproteinemia Type II as compared to allele A.
Notes: No significant association was found between changes in cholesterol levels or triglycerides and this SNP.
Article: Is It Time for Systematic Voriconazole Pharmacogenomic Investigation for Central Nervous System Aspergillosis?
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): voriconazole
Phenotype category: Efficacy
Significant: not stated
Association: CYP2C19 *1/*17 is associated with decreased response to voriconazole in people with Mycoses.
Notes: Case report. A 39-year-old woman developed central nervous system aspergillosis. She was treated with therapeutic drug monitoring-guided voriconazole therapy. Optimal trough concentrations were difficult to reach despite very high doses of voriconazole. Caspofungin was added, and voriconazole dose was increased to 400mg t.i.d. The patient was then found to be heterozygous for the CYP2C19*17 variant. One month after combined and adjusted dose of voriconazole, patient had clinical improvement. Authors state that this CYP2C19 mutation was "partially responsible for the therapeutic failure of voriconazole".
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: TRPV1
Variant/haplotype: rs222747
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele G.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: HTR2C
Variant/haplotype: rs3813928
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to risperidone in people with Schizophrenia as compared to allele G.
Article: Analysis of Genetic and Clinical Factors Associated with Buprenorphine Response
Variant/haplotype: rs13169373
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to buprenorphine in people with Opioid-Related Disorders as compared to allele C.
Notes: Authors note that this association is nominally significant.
Article: Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR long form (L allele), SLC6A4 HTTLPR short form (S allele)
Drug(s): buprenorphine, methadone
Phenotype category: Efficacy
Significant: yes
Association: SLC6A4 HTTLPR short form (S allele)/HTTLPR short form (S allele) is associated with decreased response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to SLC6A4 HTTLPR long form (L allele)/HTTLPR long form (L allele) + HTTLPR long form (L allele)/HTTLPR short form (S allele).
Notes: Response defined by changes in the rate of dropout from treatment between genotypes. Authors designate this association as nominally significant as significance was lost following correction for multiple testing.
Article: Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease
Gene: RASGRP2
Variant/haplotype: rs2230414
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with increased resistance to clopidogrel in people with Coronary Disease as compared to allele G.
Notes: alleles complemented.
Article: Fixed dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer
Gene: DPYD
Variant/haplotype: rs1801159
Drug(s): capecitabine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of capecitabine in people with Breast Neoplasms as compared to allele T.
Notes: No significant differences in the area under the concentration-time curve from 0 to infinity (AUCinf) were seen between any of the genotypes (CC, CT, TT). Nor were any significant differences seen between these genotypes when considering the capecitabine metabolites 5'-DFCR, 5'-DFUR or 5'FU (5'-fluorouracil). Please note alleles have been complemented to the plus chromosomal strand.
Article: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
Gene: PPARD
Variant/haplotype: rs6922548
Drug(s): docetaxel, thalidomide
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to docetaxel and thalidomide in people with Prostatic Neoplasms as compared to allele A.
Notes: (allele inferred by frequency comparison with dbSNP, actual base not listed in paper)
Article: Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery
Gene: UGT2B7
Variant/haplotype: rs7668282
Drug(s): fentanyl
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele T.
Notes: There was no significant difference in 24 hour fentanyl use between the genotype groups.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: RRP7A
Variant/haplotype: rs11553441
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: CYP2B6
Variant/haplotype: rs3745276
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AG is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype GG.
Notes: from TABLE 4 Ticagrelor pharmacokinetic parameters based on genotypes without statistical significance and TABLE 5; AR-C124910XX pharmacokinetic parameters based on genotypes without statistical significance
Article: Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives – Results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: FGF5
Variant/haplotype: rs1458038
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Genotypes CT + TT are not associated with response to atenolol in people with Hypertension as compared to genotype CC.
Notes: Not significant when using Bonferroni-corrected alpha of 0.0014. Response was assessed by change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 9 weeks of treatment.
Article: Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder
Gene: ADH1B
Variant/haplotype: rs2066702
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to naltrexone in men with Alcoholism as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand. The A allele is also referred to as the ADH1B*3 allele in the paper. Patients carrying the A allele reported more drinking days during naltrexone treatment.
Article: Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway
Gene: RGS17
Variant/haplotype: rs672170
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to antidepressants in people with Depressive Disorder, Major as compared to allele G.
Notes: Identity of minor allele not specified, so minor allele of dbSNP used here. Remission considered to be score < or equal to 7 at discharge of the Hamilton Rating Scale for Depression (HRSD17). Patients measured at admission and discharge, 4-6 weeks later. Specific antidepressants not listed.
Article: Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer
Gene: SLC47A1
Variant/haplotype: rs2289669
Drug(s): tipiracil hydrochloride, trifluridine
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to tipiracil hydrochloride and trifluridine in people with Colorectal Neoplasms as compared to allele G.
Notes: The SNP was tested for association alone and with three other SNPs after univariate and multivariate analysis in a training (N= 52, Japan) and testing cohorts (N = 127, Italy). It was not significant with progression-free or overall survival in either cohorts.
Article: Characterizing variability in warfarin dose requirements in children using modelling and simulation
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): warfarin
Phenotype category: Dosage, Efficacy
Significant: yes
Association: CYP2C9 *2/*2 is associated with decreased dose of warfarin in children with Heart Diseases as compared to CYP2C9 *1/*1.
Notes: A model was created to predict maintenance doses for children of different ages, all with a baseline INR of 1 and a target INR of 2.5, based on longitudinal data from children taking warfarin. Due to the nature of the model, the quantitative CYP2C9 allele effects on clearance were assumed to be the same as for adults - n=2 children had the *2/*2 genotype in the data cohort. CYP2C9 genotype, VKORC1 genotype, bodyweight, age, baseline INR, target INR and time since initiation of therapy were all found to be significant causes of warfarin dose variability in children. This association is based on a table presenting results from the model predicting warfarin dose for children of 2, 8 and 14 years old with different rs9923231 genotype and CYP2C9 genotype presented in the paper. CYP2C9*2 was defined as rs1799853 and *3 as rs1057910.
Article: Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives – Results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: CHIC2
Variant/haplotype: rs871606
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to atenolol in people with Hypertension as compared to allele C.
Notes: Not significant when using Bonferroni-corrected alpha of 0.0014. Response was assessed by change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 9 weeks of treatment.
Article: IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection
Variant/haplotype: rs10853728
Drug(s): peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes CC + CG.
Notes: This genotype has decreased association with sustained virological response (SVR).
Article: A Common Susceptibility Gene for Type 2 Diabetes Is Associated with Drug Response to a DPP-4 Inhibitor: Pharmacogenomic Cohort in Okinawa Japan
Gene: CDKAL1
Variant/haplotype: rs7756992
Drug(s): Dipeptidyl peptidase 4 (DPP-4) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to Dipeptidyl peptidase 4 (DPP-4) inhibitors in people with Diabetes Mellitus as compared to allele A.
Notes: The SNP was significantly associated with improved response to DPP-4 inhibitors (as assayed by reductions in HbA1c). Most of the patients were on combination anti-diabetic agent (ADA) therapy, but the relationship was only significant for regimens that included DPP-4 (alone or in combination with other ADAs).
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: OPRM1
Variant/haplotype: rs1323040
Drug(s): sufentanil
Phenotype category: Dosage
Significant: yes
Association: Genotypes AG + GG are associated with increased dose of sufentanil in people with Lung Neoplasms and Pain, Postoperative as compared to genotype AA.
Notes: Patients with the GG genotype had significantly increased sufentanil consumption compared to patients with the AA or AG genotypes, while those with the AG genotype had significantly increased compared to patients with the AA genotype.
Article: Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy
Gene: CYP19A1
Variant/haplotype: rs2289105
Drug(s): triglycerides
Phenotype category: Other
Significant: yes
Association: Allele C is associated with decreased concentrations of triglycerides in women with Breast Neoplasms and Menopause as compared to allele T.
Notes: when taking letrozole alone or with lipid lowering agents (LLA), such as statins. Data are from a sub-analysis of the Exemestane and Letrozole Pharmacogenomics (ELPh) study, where post-menopausal women with early stage breast cancer were randomized to receive exemestane or letrozole. Of the 303 eligible women, 160 were randomized to the letrozole group, 52 of whom were also taking LLA. This SNP was associated with decreases in triglycerides of 36.45 mg/dL (SE 7.8).
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: ABCB1
Variant/haplotype: rs1045642
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AG are not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
Notes: There is no association between selected SNPs and methotrexate plasma level at 48 h between the first dose of methotrexate infusion. med. MTX concentration: AG+AA (0.41 (0.12–41.63)) vs. GG (0.46 (0.09–10.88)). Please note: alleles have been complemented to the + chromosomal strand.
Article: Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition
Gene: SLCO1B1
Variant/haplotype: SLCO1B1*1, SLCO1B1*31, SLCO1B1*37
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: SLCO1B1 *31 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: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs495491
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele A.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole
Gene: SLCO1B1
Variant/haplotype: rs10841753
Drug(s): estrone sulfate
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased concentrations of estrone sulfate in women with Breast Neoplasms as compared to allele T.
Notes: when treated with aromatase inhibitors. Authors describe association for number of "variant allele" compared to "wild type" and in figure 2 show "wild type" as TT. "Each rs10841753 variant allele was associated with a decreased risk of failing to achieve undetectable E1S concentrations after 3 months of AI therapy however, there was no significant effect on E1 or E2" stratified analysis showed was confined to the exemestane arm not letrozole arm.