shlokn/autogkb huggingface dataset:
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: GABRA3
Variant/haplotype: rs6627221
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 T.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma
Gene: HSD3B1
Variant/haplotype: rs1047303
Drug(s): glucocorticoids
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AC are associated with increased resistance to glucocorticoids in people with Asthma as compared to genotype CC.
Notes: The adrenal restrictive allele (A) is linked to reduced conversion of DHEA to androgen and poorer-than-usual treatment response and reduced forced expiratory volume, a measure of lung function. In contrast, patients who carried two copies of a "permissive" HSD3B1 allele (CC) had increased conversion to androgen and were not associated with reduced lung function in patients with or without daily oral glucocorticoid treatment.
Article: CYP2C9*1B Promoter Polymorphisms, in Linkage with CYP2C19*2, Affect Phenytoin Autoinduction of Clearance and Maintenance Dose
Gene: CYP2C9
Variant/haplotype: rs71486745
Drug(s): warfarin
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Allele del is not associated with dose of warfarin in people with stable INRs in target range of 2-3 as compared to allele GT.
Notes: after excluding those patients carrying CYP2C9*2, *3, and VKORC1 variant alleles.
Article: Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective
Gene: NR1I2
Variant/haplotype: rs3732357
Drug(s): rifampin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG is associated with decreased exposure to rifampin in people with Tuberculosis as compared to genotype GG.
Notes: "However, a relationship was found between one of the NR1I2 gene intronic polymorphisms, i.e., rs3732357, and RIF plasma exposure: the results showed that patients with the GA/AA genotype had lower RIF AUC0–6 h in comparison to the GG genotype (p = 0.026)."
Article: Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia
Gene: ABCC4
Variant/haplotype: rs2274407
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.
Notes: All patients received four cycles of high dose MTX (5000mg per square meter of body surface area). 1/10th of the dose was administered over 30 minutes (rapid infusion) and the rest was administered continuously over 24hrs. Leucovorin rescue was administered every 6hrs starting 48 hrs after initiation of MTX infusion.
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): noroxymorphone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 poor metabolizer is associated with decreased concentrations of noroxymorphone in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: Cmax and AUC for noroxymorphone were significantly lower in poor metabolizers than in extensive metabolizers.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: ABCC2
Variant/haplotype: rs3740066
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele C.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.
Article: The KCNH2 Genetic Polymorphism (1956, C>T) Is a Novel Biomarker That Is Associated with CCB and α,β-ADR Blocker Response in EH Patients in China
Gene: KCNH2
Variant/haplotype: rs1137617
Drug(s): atenolol, bisoprolol, celiprolol, doxazosin
Phenotype category: Efficacy
Significant: not stated
Association: Genotype GG is associated with response to atenolol, bisoprolol, Celiprolol or doxazosin in people with Essential hypertension as compared to genotypes AA + AG.
Notes: however the analysis solely comparing genotypes is not shown and stats are given for GG genotype x gender or age comparisons.
Article: Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma
Gene: SLC19A1
Variant/haplotype: rs1051266
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with decreased concentrations of methotrexate in children with Osteosarcoma as compared to genotype CC.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Pharmacogenetics of unboosted atazanavir in HIV-infected individuals in resource-limited settings: a sub-study of the AIDS Clinical Trials Group (ACTG) PEARLS study (NWCS 342)
Gene: CYP3A5
Variant/haplotype: CYP3A5 deficiency
Drug(s): atazanavir
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 deficiency is not associated with concentrations of atazanavir in people with HIV as compared to CYP3A5 non-deficient.
Notes: Genotypes assessed were CYP3A5*3 (rs776746) and CYP3A5*6 (rs10264272), and categorized as expresser and non-expresser. Looked at ratios of metabolites to atazanavir.
Article: Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment
Variant/haplotype: rs1247117
Drug(s): vincristine
Phenotype category: PD
Significant: not stated
Association: Allele G is associated with increased resistance to vincristine as compared to allele A.
Notes: "the risk G allele at rs1247117 was also associated with vincristine resistance in primary ALL cells from patients"
Article: Association of single nucleotide polymorphisms in MTHFR and ABCG2 with the different efficacy of first-line chemotherapy in metastatic colorectal cancer
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): antineoplastic agents
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to antineoplastic agents in people with Colorectal Neoplasms as compared to genotypes GT + TT.
Notes: Patients with the GG genotype receiving a FOLFOX/XELOX regimen (respectively: fluorouracil, leucovorin, oxaliplatin; capecitabine, oxaliplatin) had a decreased response rate, as compared to those with the GT or TT genotype. No significant difference in response rate was seen in patients receiving a FOLFIRI regimen (fluorouracil, leucovorin, irinotecan). No significant differences in progression-free survival were seen for either regimen. Please note alleles have been complemented to the plus chromosomal strand.
Article: Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population
Gene: CHRNA5
Variant/haplotype: rs6495306
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele G is not associated with exposure to nicotine in men as compared to allele A.
Notes: The G allele was initially associated with an increased likelihood of being a smoker but this lost significance following correction for multiple testing.
Article: Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention
Gene: ABCC2
Variant/haplotype: rs717620
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to clopidogrel in people with Coronary Artery Disease as compared to genotypes CT + TT.
Article: Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype AC is associated with decreased dose of warfarin as compared to genotype AA.
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: CHRNA3
Variant/haplotype: rs6495307
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele T 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: Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9
Gene: CYP2C8
Variant/haplotype: rs11572080
Drug(s): piroxicam
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is not associated with response to piroxicam as compared to allele C.
Notes: Subjects had at least one impacted lower third molar extracted. Measurements were taken of 1) postoperative mouth opening (millimeters) was measured pre- and post-op on days 2 & 7 2) and swelling measurements due to edema were recorded and 3) subjective measures of pain. None were associated with the genotype.
Article: Real‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry
Gene: CYP2D6
Variant/haplotype: CYP2D6 ultrarapid metabolizer
Drug(s): eliglustat
Phenotype category: Dosage
Significant: not stated
Association: CYP2D6 ultrarapid metabolizer is associated with increased dose of eliglustat in people with Gaucher Disease as compared to CYP2D6 intermediate metabolizer and normal metabolizer.
Notes: Six patients in the study cohort were determined to be CYP2D6 ultrarapid metabolizers, four of whom recorded an eliglustat dose of 84mg three times daily, while the recommended dose for normal and intermediate metabolizers is 84mg twice daily. Note that eliglustat is not approved for use in CYP2D6 ultrarapid metabolizers. The paper does not detail how CYP2D6 phenotypes were determined.
Article: Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased concentrations of tacrolimus in people with Kidney Transplantation as compared to genotypes AC + CC.
Notes: "Patients carrying the AA genotype from the ABCB1 2677 group tend to have lower concentrations than those without the AA genotype, as indicated by the lower mean rank (29.67 vs. 8.33) and p-value = 0.005 (Figure 2)." "Genotype analysis revealed that the AA genotype of ABCB1 G2677A was significantly associated with Tc levels within the normal range (p = 0.0111; PFDR = 0.0334; 95% C.I. = 0.01–0.08)."
Article: Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis
Gene: GLP1R
Variant/haplotype: rs6923761
Drug(s): sitagliptin
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to sitagliptin in people with Diabetes Mellitus, Type 2.
Notes: "Regarding GLP1R gene polymorphisms, patients with the rs6923761 AA homozygous genotype in the study group had a median HbA1c improvement of 0.90 (IQR, 0.61–1.01), while the control group showed 1.41 (IQR, 1.12–1.45; P = .010), suggesting reduced glycemic response to sitagliptin."
Article: Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to allele T.
Notes: Trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in rs 2740574 TT genotype (CYP3A4*1/*1) compared to CT and CC genotypes (CYP3A4*1B carriers) at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation.
Article: Characterization of raloxifene glucuronidation. Potential role of UGT1A8 genotype on raloxifene metabolism in vivo
Gene: UGT1A8
Variant/haplotype: UGT1A8*1a, UGT1A8*2, UGT1A8*3
Drug(s): raloxifene
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A8 *1a/*3 (assigned as poor metabolizer phenotype) is associated with increased metabolism of raloxifene in women as compared to UGT1A8 *1a/*1a + *1a/*2 + *2/*2 (assigned as intermediate metabolizer and normal metabolizer phenotype) .
Notes: Those with the *1/*3 genotype (slow raloxifene metabolizers) had decreased dose-adjusted raloxifene metabolite levels in plasma, as compared to those with the *1/*1 and *1/*2 genotypes (intermediate metabolizers) and the *2/*2 genotype (fast metabolizers). Metabolites included raloxifene-6-glucuronide, raloxifene-4'-glucuronide and total raloxifene-glucuronide. Subjects were either given 30 or 60mg of raloxifene.
Article: Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients
Gene: IL10
Variant/haplotype: rs1800872
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with dose-adjusted trough concentrations of tacrolimus in people with lung transplantation as compared to genotypes GG + GT.
Notes: No significant difference in dose-adjusted trough concentration was seen between patients with the TT genotype and those with the GG + GT genotypes at weeks 1, 2, 3 or 4 post-transplant. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population
Gene: CHRNA5
Variant/haplotype: rs555018
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele G is not associated with exposure to nicotine in men as compared to allele A.
Notes: The G allele was initially associated with an increased likelihood of being a smoker but this lost significance following correction for multiple testing.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: P2RX7
Variant/haplotype: rs2230912
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele A.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Genome-wide association study of warfarin maintenance dose in a Brazilian sample
Gene: VKORC1
Variant/haplotype: rs749671
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele G is associated with increased dose of warfarin as compared to allele A.
Notes: The G allele was strongly associated with high warfarin dose (G allele, OR: 20.4 [14.3–29.0]; p = 1.08 × 10-33) in Brazilian patients.
Article: Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders
Gene: DRD1
Variant/haplotype: rs4867798
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to methylphenidate in children with Autism Spectrum Disorder as compared to genotype TT.
Notes: Positive response defined as Clinical Global Impression-Improvement (CGI-I) rating of 'much improved' or 'very much improved', and decrease in Aberrant Behavior Checklist-Hyperactivity subscale of >25% from baseline. This result was not significant when considering correction for multiple testing (p<0.002). Please note that alleles have been complemented to the plus chromosomal strand.
Article: Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizers and intermediate metabolizers
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 poor metabolizers and intermediate metabolizers are associated with increased trough concentration of voriconazole in people with Mycoses as compared to CYP2C19 normal metabolizer.
Notes: Poor metabolizers = PMs (n=7); Intermediate metabolizers = IMs (n=24); Extensive metabolizers = EMs (n=30); Ultrarapid metabolizers = UMs (n=14). Patients were liver transplant recipients with known or suspected invasive fungal infections.
Article: A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering
Gene: TOMM40
Variant/haplotype: rs2075650
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to hmg coa reductase inhibitors as compared to allele A.
Notes: as part of a three SNP genetic risk score with rs2231142 in ABCG2 and rs10455872 in LPA. Associated allele not explicitly stated but methods reference Chasman et al., so used the associated allele from there [PMID:22331829].
Article: Pharmacogenetics of Asthma Controller Treatment
Gene: CRHR1
Variant/haplotype: rs739645
Drug(s): fluticasone propionate
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to fluticasone propionate in people with Asthma as compared to allele T.
Notes: The minor allele is reported to be associated with increased response.
Article: Underlying genetic structure impacts the association between CYP2B6 polymorphisms and response to efavirenz and nevirapine
Gene: CYP2B6
Variant/haplotype: rs1042389
Drug(s): efavirenz, non-nucleoside reverse transcriptase inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to efavirenz or non-nucleoside reverse transcriptase inhibitors in women with HIV Infections as compared to genotype TT.
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Variant/haplotype: rs4815273
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele C.
Notes: The association was with systolic blood pressure response. Observations: 2.91 mm Hg increased reduction of systolic blood pressure per T allele in PEAR + GERA, 0.39 mm Hg increased reduction of systolic blood pressure per T allele in NORDIL, and 2.34 mm Hg increased reduction of systolic blood pressure per T allele in PEAR + GERA + NORDIL.  This association was significant in PEAR + GERA but not in the replication cohort NORDIL nor in the 3 cohort meta-analysis.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs1302192284
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele C is associated with decreased metabolism of nicotine as compared to allele T.
Notes: Assigned as loss-of-function following in vitro assessments, in vivo associations and variant construct functional assignments.
Article: Prognostic Role of Human Leukocyte Antigen Alleles and Cytokine Single-Nucleotide Polymorphisms in Patients with Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitor Drugs
Gene: HLA-A
Variant/haplotype: HLA-A*23:17
Drug(s): BCR-ABL tyrosine kinase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: HLA-A *23:17 is associated with decreased clinical benefit to BCR-ABL tyrosine kinase inhibitors in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive.
Notes: "In the treated cohorts, we found less HLA-A*23:17:01 (p-value = 0.0285) in the favorable group compared to the unfavorable group." Zero *23:17 were reporteded in the favorable group in Table 4
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: PRKAB2
Variant/haplotype: rs7541245
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
Notes: "he Locus Zoom plot for PRKAB2 (Supplementary Figure 1) placed rs7541245, the most significant (p=0.0019) SNP, as outside the gene boundaries. 5 SNPs (rs6665580, rs6659191, rs6678588, rs7541245, rs10494243) in high LD within PRKAB2, were found to be significantly associated with a decrease in glycemic response after metformin exposure. In summary, variation in PRKAB2, the gene encoding the beta subunit 2 of adenosine monophosphate-activated protein kinase complex, appears to be associated with decreases in glycemic response after exposure to metformin, with rs7541245 having the strongest SNP association." Authors looked at candidate genes in patients that had previously had genome sequencing. They look quite far outside of conventional gene boundaries. "For each candidate gene we selected SNPs 50 kb upstream and downstream of each gene using 1000 genomes project variants and NCBI build 37 as the reference genome."
Article: Population Pharmacokinetic Modeling of the Association between 63396C→T Pregnane X Receptor Polymorphism and Unboosted Atazanavir Clearance
Gene: NR1I2
Variant/haplotype: rs2472677
Drug(s): atazanavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased metabolism of atazanavir in people with HIV Infections as compared to genotypes CC + CT.
Notes: TT was associated with 17% higher clearance of unboosted atazanavir.
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: LRP1B
Variant/haplotype: rs874295
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with response to risperidone in people with Schizophrenia.
Notes: as measured by changes in PANSS-T (positive and negative syndrome scale total score), using a mixed model repeated measures approach. Examined 6789 SNPs - p-value of p< or equal to 5x10-4 was considered significant. Please note: reported allele was C, this has been complemented to the plus chromosomal strand. It was unclear whether the allele was associated with an increased or decreased response to drug.