shlokn/autogkb huggingface dataset:
Article: Individualized atomoxetine response and tolerability in children with ADHD receiving different dosage regimens: the need for CYP2D6 genotyping and therapeutic drug monitoring to dance together
Gene: CYP2D6
Variant/haplotype: CYP2D6*10
Drug(s): atomoxetine
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 *10/*10 (assigned as intermediate metabolizer phenotype) is associated with increased clinical benefit to atomoxetine in children with Attention Deficit Disorder with Hyperactivity as compared to CYP2D6 normal metabolizer.
Notes: "As expected, CYP2D6 IMs demonstrated a better clinical response than those EMs due to the higher drug exposure under q.m. dosing regimen (Table ​(Table3).3). However, statistically significant differences of concentrations (Fig. 4B, C), cut-off values (Fig. 4E-F), and clinical response were not found under the other two dosing regimens, possibly due to the small sample size." The regimens were qm (once morning), bid (twice daily) and qn (once nightly). Study measured CYP2D6*2, CYP2D6*10, and CYP2D6*14 and grouped *10/*10 as intermediate. There was only one PM that was excluded from analysis.
Article: Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele C.
Notes: It is assumed that the alleles are reported in the paper as being on the positive strand.
Article: Variant‐based heritability assessment of dexmedetomidine and fentanyl clearance in pediatric patients
Gene: CACNB2
Variant/haplotype: rs560765906
Drug(s): dexmedetomidine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is associated with decreased clearance of dexmedetomidine in children with Pain, Postoperative as compared to allele A.
Notes: Data from Table S2, direction of effect and risk allele not clear. Minor allele and frequency stated. Mapped to dbSNP using genomic location 10:18437025:A:T on hg19/GRCh37. "GWAS failed to identify any variants meeting the genome-wide statistical significance threshold of 5 × 10−8" This is second highest scoring variant.
Article: Genetic Polymorphism of Inosine Triphosphate Pyrophosphatase Is a Determinant of Mercaptopurine Metabolism and Toxicity During Treatment for Acute Lymphoblastic Leukemia
Gene: ITPA
Variant/haplotype: rs1127354
Drug(s): mercaptopurine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with metabolism of mercaptopurine in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.
Notes: The A allele was associated with increased methylmercaptopurine nucleotide metabolite concentration in bone marrow leukemia cells. Concentrations were also found to be significantly higher in erythrocytes of patients with an A allele during continuation therapy with mercaptopurine.
Article: CYP4F2 Is a Vitamin K1 Oxidase: An Explanation for Altered Warfarin Dose in Carriers of the V433M Variant
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin as compared to allele C.
Notes: TT > CT > CC.
Article: Enantiospecific Pharmacogenomics of Fluvastatin
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): fluvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 *2 is associated with increased concentrations of fluvastatin in healthy individuals as compared to CYP2C9 *1/*1.
Notes: This variant is significantly associated with increased area under the plasma concentration-time curve (AUC) of both 3R,5S-fluvastatin and 3S,5R-fluvastatin and total fluvastatin in the candidate gene study.
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs529520
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to buprenorphine in people with Opioid-Related Disorders as compared to allele A.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.; Please note that alleles have been complemented to the positive strand.
Article: Impact of ABCC2 1249G>A and −24C>T Polymorphisms on Lacosamide Efficacy and Plasma Concentrations in Uygur Pediatric Patients With Epilepsy in China
Gene: ABCC2
Variant/haplotype: rs717620
Drug(s): lacosamide
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased concentrations of lacosamide in children with Epilepsy as compared to genotypes CT + TT.
Article: Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies
Gene: CHRNA5
Variant/haplotype: rs55781567
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to bupropion, nicotine and varenicline in people with Tobacco Use Disorder as compared to allele C.
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: An expanded pharmacogenomics warfarin dosing table with utility in generalised dosing guidance
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele A is associated with dose of warfarin as compared to allele G.
Notes: This variant annotation is part of a dosing algorithm table based on 8 genetic variants.
Article: Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta‐Analysis
Gene: SLC22A4
Variant/haplotype: rs1050152
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
Notes: This variant is not associated with metformin glycemic response assessed as HbA1c reduction in patients on metformin monotherapy.
Article: Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): nevirapine
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Genotypes AA + AG are not associated with decreased clearance of nevirapine in people with HIV Infections as compared to genotype GG.
Notes: no association with PK parameters area under the concentration time curve or apparent oral clearance of the drug. [stat_test: univariate and multiple linear regression]
Article: Potential role of PIN1 genotypes in predicting benefit from oxaliplatin- and irinotecan-based treatment in patients with metastatic colorectal cancer
Gene: TP53
Variant/haplotype: rs1042522
Drug(s): oxaliplatin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CG + GG is associated with decreased response to oxaliplatin in people with Colorectal Neoplasms as compared to genotype CC.
Notes: Patients receiving FOLFOX (oxaliplatin+fluorouracil+leucovorin) with or without bevacizumab. No significant association with progression-free survival or overall survival was seen.
Article: SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): capecitabine, fluorouracil, irinotecan, leucovorin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to capecitabine, fluorouracil, irinotecan or leucovorin in people with Colorectal Neoplasms as compared to genotype GG.
Notes: Patients were split into two groups based on treatment. One group received irinotecan, fluorouracil, and leucovorin, and the other group received irinotecan and capecitabine. Patients carrying the A allele showed significantly greater rapid response rate, progression free survival, and irinotecan-related time to treatment failure as compared to patients with the GG genotype. In addition, when combined with rs1051266, patients carrying the A allele for this SNP and homozygous for the G allele at rs1051266 had significantly higher rapid response rates than patients with any other combination of genotypes.
Article: Characterization of a Novel BCHE “Silent” Allele: Point Mutation (p.Val204Asp) Causes Loss of Activity and Prolonged Apnea with Suxamethonium
Gene: BCHE
Variant/haplotype: BCHE deficiency
Drug(s): succinylcholine
Phenotype category: Toxicity, Other
Significant: no
Association: BCHE deficiency is associated with decreased metabolism of succinylcholine.
Notes: This is a case report of prolonged neuromuscular block after administration of suxamethonium and to the discovery of a novel BCHE deficiency variant, c.695T>A, p.Val204Asp.
Article: Pharmacogenetic Predictors of Cannabidiol Response and Tolerability in Treatment‐Resistant Epilepsy
Variant/haplotype: rs6729738
Drug(s): cannabidiol
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to cannabidiol in people with Epilepsy as compared to genotypes AA + AC.
Notes: Patients carrying the C allele of the variant were were likely to respond to cannabidiol in patients with treatment-resistant epilepsy (TRE).
Article: Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*4
Drug(s): amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline, opipramol
Phenotype category: Toxicity
Significant: no
Association: CYP2D6 *4/*4 is not associated with discontinuation of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline and opipramol in people with Depression as compared to CYP2D6 *1/*1.
Notes: (*4*4 vs. *1*1; this SNP was the only SNP assayed and this method could not detect *5.) Tricyclic antidepressants were grouped together for this analysis (45.9 % of patients were taking Amitriptyline; 8.2% Maprotiline;6.6% Clomipramine; 2.9% Nortriptyline;2.4% Imipramine;0.7% Dosulepin;0.3% Doxepin;0.2% Opipramol.  No differences in discontinuation of antidepressants below 45 days was found.
Article: Population Pharmacokinetic and Pharmacogenetic Analysis of Nevirapine in Hypersensitive and Tolerant HIV-Infected Patients from Malawi
Gene: CYP2B6
Variant/haplotype: rs28399499
Drug(s): nevirapine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype CT is associated with decreased clearance of nevirapine in people with HIV Infections as compared to genotype TT.
Notes: Those with the CT genotype had a 33% reduction in clearance of nevirapine as compared to those with the TT genotype. This SNP remained in the multiple SNP analysis model after backwards elimination.
Article: Genomewide Association Study Identifies Novel Genetic Loci That Modify Antiplatelet Effects and Pharmacokinetics of Clopidogrel
Gene: ABCA1
Variant/haplotype: rs2487032
Drug(s): clopidogrel
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased metabolism of clopidogrel as compared to genotype GG.
Notes: This variant was associated increased the concentration of plasma clopidogrel’s active metabolite H4 and increased inhibition of platelet function. However, it was not associated with clinical outcome of clopidogrel.
Article: Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real‐life clinical practice
Gene: IL17RC
Variant/haplotype: rs708567
Drug(s): tildrakizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased clinical benefit to tildrakizumab in people with Psoriasis as compared to genotypes CT + 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." Table 2, 3 and figure 1 show CC as the genotype associated with improved response.
Article: Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes
Gene: VEGFA
Variant/haplotype: rs699947
Drug(s): VEGF/VEGFR (Vascular Endothelial Growth Factor) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AC + CC is associated with increased response to VEGF/VEGFR (Vascular Endothelial Growth Factor) inhibitors in people with Macular Degeneration as compared to genotype AA.
Notes: "Also, we found that rs699947 heterozygous and homozygous minor allele carriers had higher CMT after 6 months of anti-VEGF treatment than wild-type genotype carriers (p = 0.032) (Table 4). However, the results did not remain statistically significant after the Bonferroni correction was applied." "In VEGFA SNVs and anti-VEGF treatment response analysis, we found that rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.027; p = 0.003; p = 0.022, respectively). Because of the Bonferroni correction, statistical significance was maintained only in the analysis of the genotype and BCVA results after 3 months of treatment."
Article: Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics
Gene: UGT1A3
Variant/haplotype: rs7604115
Drug(s): montelukast
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased concentrations of montelukast in healthy individuals as compared to allele C.
Notes: This UGT1A3 intronic variant is associated with reduced area under the plasma concentration-time curve (AUC) of montelukast (by 18% per copy of the minor allele; P=1.83 × 10-10). This variant is strongly linked with UGT1A3*2 which is associated with increased UGT1A3 expression.
Article: Effect of UGT2B10, UGT2B17, FMO3, and OCT2 Genetic Variation on Nicotine and Cotinine Pharmacokinetics and Smoking in African Americans
Gene: FMO3
Variant/haplotype: rs2266782
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of nicotine in people with Tobacco Use Disorder as compared to allele A.
Notes: This SNP is not associated with the pharmacokinetic measures of nicotine. Measures include half-life, Cmax, AUC, non renal clearance, and total clearance.
Article: The Relation Between CYP2C19 Genotype and Phenotype in Stented Patients on Maintenance Dual Antiplatelet Therapy
Gene: CYP2C19
Variant/haplotype: rs12248560
Drug(s): aspirin, clopidogrel
Significant: yes
Association: Allele T is associated with increased response to aspirin and clopidogrel in people with Coronary Artery Disease as compared to allele C.
Notes: For 20 microMolar ADP-induced platelet aggregation, the prevalence of High Platelet Reactivity (HPR) was lower in (TT +TC) vs CC, but the template doesn't accommodate this.  *17 SNP.  For 5 microMolar ADP-induced platelet aggregation, the association was NOT significant ( p = 0.32).  [stat_test: chi-square]
Article: ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Gene: ADH1B
Variant/haplotype: rs2018417
Drug(s): ethanol
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Allele A is associated with metabolism of ethanol.
Notes: The authors did not report p-value correction for multiple hypotheses (103 snps tested).  Though they report multiple snps are significantly associated with alcohol metabolism (early or late) tested on blood or breath alcohol concentrations, this snp is NOT significant after Bonferroni correction (<0.00049).  Also, the authors did not state which alleles are associated with increased or decreased metabolism.  Instead, they simply report an association with the snp in general.  Note that this gene is on the minus strand.
Article: Genome-Wide Pharmacogenomic Study of Neurocognition As an Indicator of Antipsychotic Treatment Response in Schizophrenia
Gene: SLC26A9
Variant/haplotype: rs11240594
Drug(s): olanzapine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele A is associated with increased response to olanzapine in people with Schizophrenia as compared to allele G.
Notes: Adjacent SNPs also showed evidence for association.  Associated allele is not clear; it is reported as the minor allele being associated with greater response.  dbSNP shows A to generally be the minor allele, but this is not the case in all populations.  Most of the study participants were of White or Black ancestry (for which A is reported to be the minor allele), but only a study subset was genotyped, and the population distribution is not clear.  GWAS p =1.4 x 10 (-7) for 492K SNPs, so Bonferroni-corrected p is 0.068 .
Article: Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): everolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AA + AC are not associated with concentrations of everolimus in women with Breast Neoplasms as compared to genotype CC.
Notes: Please note: alleles have been complemented to the positive chromosomal strand.
Article: Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery
Gene: UGT2B7
Variant/haplotype: rs4296738
Drug(s): fentanyl
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele G.
Notes: There was no significant difference in 24 hour fentanyl use between the genotype groups.
Article: Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test
Gene: ATF2
Variant/haplotype: rs7583431
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 A.
Article: Pharmacodynamic Modeling of Warfarin Dosing Algorithm for Cardiovascular Patients in Indonesia: A Tailored Method to Anticoagulation Therapy
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin in people with Rheumatic Heart Disease, Atrial Fibrillation, Heart Valve Diseases or Coronary Artery Disease.
Notes: "The Kruskal–Wallis test on genotype showed a p-value of 0.02 (<0.05), suggesting that the CC, CT, and TT genotypes have a significant association with warfarin dosage. " "Dosing based on the CYP4F2 rs2108622 genetic polymorphism showed that patients with CC, CT, and TT genotypes required doses of 19 mg, 21 mg, and 33 mg, respectively. "
Article: Absorption of Montelukast is Transporter Mediated: a Common Variant of OATP2B1 is Associated with Reduced Plasma Concentrations and Poor Response
Gene: SLCO2B1
Variant/haplotype: rs2306168
Drug(s): montelukast
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to montelukast in people with Asthma as compared to allele T.
Notes: Also not associated with plasma concentration of montelukast.
Article: Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase‐driven adaptive dosing of 5‐FU in patients with digestive cancer
Gene: DPYD
Variant/haplotype: DPYD poor metabolizer
Drug(s): fluorouracil
Phenotype category: Dosage
Significant: yes
Association: DPYD poor metabolizer is associated with decreased dose of fluorouracil in people with Colorectal Neoplasms, Gastrointestinal Neoplasms and Rectal Neoplasms as compared to DPYD normal metabolizer.
Notes: The study was an attempt to verify a novel assay to phenotype DPYD enzyme activity. DPYD deficiency was based on monitoring endogenous dihydrouracil to uracil (UH2/U) ratio in plasma after standard liquid-liquid extraction using  HPLC-UV. Ratio values were used to determine DPD status as a continuous variable and because no mathematical model was available, patients were categorized on UH2/U ratio values into poor (mild, intermediate, profound) or extensive metabolizers. Doses were tailored to a patient's UH2/U ratio determined DPYD phenotype and after dose tailoring the authors found no significant difference between clinical benefit or toxicity between PM and EM groups.
Article: CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*5, CYP2D6*6, CYP2D6*9, CYP2D6*17, CYP2D6*41
Drug(s): oxymorphone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *1/*1 + *1/*9 + *2/*9 + *1/*2 + *2/*2 (assigned as normal metabolizer phenotype) is associated with increased exposure to oxymorphone in children with as compared to CYP2D6 *1/*4 + *1/*6 + *17/*41 + *2/*4 + *2/*5 + *4/*41 (assigned as intermediate metabolizer and poor metabolizer phenotype) .
Notes: EMs were genotypes as *1/*1, *1/*9, *2A/*9, *1/*2A, *2A/*2A, IMs were *1/*4, *1/*6, *17/*41, *2A/*4, *2A/*5, PM was *4/*41.
Article: Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): simvastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT are associated with decreased response to simvastatin as compared to genotype TT.
Notes: However, the effect size was very small.
Article: Pharmacogenetic association of the APOA1/C3/A4/A5 gene cluster and lipid responses to fenofibrate: the Genetics of Lipid-Lowering Drugs and Diet Network study
Gene: APOA4
Variant/haplotype: rs675
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AT are not associated with response to fenofibrate in people with Hypertriglyceridemia as compared to genotype TT.
Notes: No significant difference in the change in plasma triglyceride (TG) or high-density lipoprotein (HDL) levels between genotypes was seen, after three weeks of treatment with fenofibrate.
Article: CBR1 and CBR3 pharmacogenetics and their influence on doxorubicin disposition in Asian breast cancer patients
Gene: CBR1
Variant/haplotype: rs20572
Drug(s): doxorubicin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with decreased exposure to doxorubicin in people with Breast Neoplasms as compared to genotype CT.
Article: High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients
Gene: ABCG2
Variant/haplotype: rs13120400
Drug(s): imatinib
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotype TT.
Notes: Individuals with the CC or CT genotype had a higher cumulative incidence of major molecular response (CI-MMR, estimated using Sokal score) after 18 months of treatment with a 400mg/day dose of imatinib, as compared to those with the TT genotype. No significant results were seen when considering patients taking a 600mg/day dose (n=107; p=0.74). The authors note that they used the Benjamini and Hochberg method for multiple testing issues.