shlokn/autogkb huggingface dataset:
Article: A functional polymorphism in the ABCB1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizer
Drug(s): morphine, nortriptyline
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 poor metabolizer is not associated with response to morphine and nortriptyline in people with Pain as compared to CYP2C19 normal metabolizer.
Notes: No significant difference in improvement in pain scores between metabolizer groups.
Article: Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes
Gene: PRKD1
Variant/haplotype: rs57803087
Drug(s): linagliptin, saxagliptin, sitagliptin, vildagliptin
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to linagliptin, saxagliptin, sitagliptin or vildagliptin in people with Diabetes Mellitus, Type 2 as compared to allele A.
Notes: "After the GWAS (stage I) and replication (stage II) results were combined, rs57803087, located within PRKD1, remained significantly associated with the DPP-4 inhibitor response (Table 4)." Effect allele is not specified in paper.
Article: Leveraging an Electronic Health Record-Linked Biorepository to Generate a Metformin Pharmacogenomics Hypothesis
Variant/haplotype: rs12752688
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to metformin in people with Diabetes Mellitus as compared to allele C.
Notes: EHR-linked and EHR-based phenotyping methods were used to study common variants within FMO5. Efficacy was assessed by A1c levels extracted from EHR records.
Article: Dose Optimization of Efavirenz Based on Individual CYP2B6 Polymorphisms in Chinese Patients Positive for HIV
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with increased clearance of efavirenz in people with HIV Infections as compared to genotypes GT + TT.
Notes: Values of oral clearance were 10.2 L/h, 7.33 L/h and 2.38 L/h for GG, GT, and TT patients, respectively.
Article: A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin as compared to allele C.
Article: Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy
Gene: ADRA2C
Variant/haplotype: rs61767072
Drug(s): Beta Blocking Agents
Phenotype category: Efficacy
Significant: yes
Association: Allele del is associated with increased response to Beta Blocking Agents in children with Cardiomyopathy, Dilated as compared to allele GGGGCGGGGCCG.
Notes: Study looked at effect of 'high-risk' genotypes (i.e. genotypes of one or more of rs61767072 del, rs1801253 C or rs1042713 A alleles) on response to beta-blockers. Patients with more 'high-risk' alleles showed a greater response to beta-blockers than those with fewer 'high-risk' alleles. Note that this variant is incorrectly referred to as rs6846820 in the paper and has been mapped to the correct rsID by PharmGKB.
Article: Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population
Gene: AGT
Variant/haplotype: rs699
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AG is not associated with exposure to atorvastatin in healthy individuals as compared to genotypes AA + GG.
Notes: The SNP was not associated with AUC, Cmax, clearance, elimination rate constant, or half-life of atorvastatin. However, the AG genotype was associated with higher AUC ad well as lower clearance of atorvastatin vs. AA or GG genotypes.
Article: SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours
Gene: SLC28A1
Variant/haplotype: rs11853372
Drug(s): gemcitabine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with metabolism of gemcitabine as compared to genotypes GG + GT.
Notes: Gemcitabine, dFdCTP, and dFdU plasma concentrations were measured before (5, 15, 30, 45 min) and after gemcitabine infusion (1, 1.25, 1.5, 2, 6, 24, 48, 72 hrs). Population pharmacokinetic analysis of gemcitabine and metabolites (dFdU, dFdCTP) were performed by non-linear mixed effects modeling. rs11853372 is not associated with metabolism of gemcitabine.
Article: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and Phe508del and a Residual Function Mutation
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor, tezacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype CTT/del is associated with increased response to ivacaftor and tezacaftor in people with Cystic Fibrosis.
Notes: This trial was designed to evaluate the efficacy and safety of tezacaftor with ivacaftor, ivacaftor monotherapy, or placebo. It is a phase 3, randomized, multicenter, double-blind, placebo-controlled, two-period, three-intervention crossover trial (NCT02392234). Patients were 12 years of age or older with cystic fibrosis (CF) and were heterozygous for the Phe508del CFTR mutation and a second allele with a CFTR mutation with residual function as assessed by in vitro studies. Each patient received two of the three regimens (tezacaftor with ivacaftor, ivacaftor monotherapy, or placebo).
Article: IFNL4 ss469415590 Variant Is Associated with Treatment Response in Japanese HCV Genotype 1 Infected Individuals Treated with IFN-Including Regimens
Gene: IFNL4
Variant/haplotype: rs11322783
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT/TT is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b, ribavirin and telaprevir in people with Hepatitis C as compared to genotypes G/TT + GG.
Notes: in Japanese hepatitis C genotype 1 patients.
Article: Novel Associations of VKORC1 Variants with Higher Acenocoumarol Requirements
Gene: VKORC1
Variant/haplotype: rs104894542
Drug(s): acenocoumarol
Phenotype category: Dosage
Significant: not stated
Association: Genotypes AC + CC is associated with increased dose of acenocoumarol as compared to genotype AA.
Notes: This variant is found in 1 patient of the group (all with higher doses than expected).
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: PRKAA1
Variant/haplotype: rs11749180
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: 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." Table 2 shows rs11749180 as top SNP for PRKAA1
Article: The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): cilostazol
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*3 (assigned as intermediate metabolizer phenotype) is associated with decreased concentrations of cilostazol in healthy individuals as compared to CYP3A5 *3/*3 (assigned as poor metabolizer phenotype) .
Notes: either when cilostazole is administered alone or in combination with clopidogrel. The authors significant differences in AUC (ng*hr/ml)  values of cilostazole metabolites when comparing between  CYP3A5 genotype groups. The differences in concentrations of cilostazole metabolite AUC between the CYP3A5 *1/*3 and CYP3A5 *3/*3 was significant when clopidogrel was administered alone or in combiation with cilostazole. Differences in the AUC (ng*hr/ml) of 4" trans hydroxy cilostazole were only significant for within genotype group comparisons between treatment (CYP3A5 *1/*3 cilostrazole only (684.33) versus cilostrazole and clopidogrel (513.85); p=0.004); CYP3A5 *3/*3 cilostrazole only (576.38) versus cilostrazole and clopidogrel (526.17); p=0.023)
Article: Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizers
Drug(s): casopitant, dolasetron
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 poor metabolizer is not associated with increased exposure to casopitant and dolasetron in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: While CYP2D6 PMs had slightly higher AUCs than CYP2D6 EMs when dolasetron was administered alone, there was no clinically relevant difference when casopitant was co-administered.; "The current study showed that coadministration of dolasetron with a 3-day regimen of casopitant resulted in no clinically relevant change in the exposure of hydrodolasetron. The largest observed changes were a 14% increase in hydrodolasetron AUC on day 1 and 18% and 22% increases in hydrodolasetron Cmax on days 1 and 3, respectively. These changes are not considered clinically relevant, were not associated with any increase in adverse events, and were within the same range of within-subject variability for dolasetron exposure."; Metabolizer status defined as: "CYP2D6 PMs (*3, *4, *5, *6, or *7 homozygotes) or CYP2D6 EMs (absence or heterozygotes for *3, *4, *5, *6, or *7 alleles and devoid of CYP2D6 gene duplication) by genotypic analysis."
Article: Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences
Variant/haplotype: rs111645190
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with metabolism of nicotine as compared to allele G.
Notes: Nicotine metabolism was assessed by measuring participants' nicotine metabolite ratio.
Article: Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients
Gene: ABCB1
Variant/haplotype: rs2235048
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are associated with increased response to risperidone in people with Schizophrenia as compared to genotype AA.
Notes: Alleles given as reverse strand C and T. Efficacy measured with reduction in PANSS total score reduced rate.
Article: Effects of CYP2C19 Loss-of-Function Variants on the Eradication of H. pylori Infection in Patients Treated with Proton Pump Inhibitor-Based Triple Therapy Regimens: A Meta-Analysis of Randomized Clinical Trials
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): omeprazole
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *1/*1 is associated with decreased response to omeprazole in people with Helicobacter Infections as compared to CYP2C19 *1/*2 + *1/*3.
Notes: Subjects with the *1/*1 genotype had a significantly lower eradication rate of Helicobacter pylori (H. pylori), as compared to those with the *1/*2 or *1/*3 genotype. This was a meta-analysis and included 6 studies. Patients were treated with the drugs anywhere from 7-14 days, and also received the antibiotics amoxicillin and clarithromycin as part of triple therapy.levofloxacin.
Article: Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome
Gene: CDK4
Variant/haplotype: rs2270777
Drug(s): somatropin recombinant
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased response to somatropin recombinant in children with growth hormone deficiency as compared to genotypes CC + CT.
Notes: Response to growth hormone treatment assessed by 1-month insulin-like growth factor-I (IGF-I) generation. Multiple test correction was done for 1171 SNPs. Corrected p values was given.
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: rs692780
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele C is not associated with exposure to nicotine in men as compared to allele G.
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: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: AQP2
Variant/haplotype: rs7305534
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to platinum in people with Lung Neoplasms as compared to allele C.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.
Article: Tacrolimus Concentration Is Effectively Predicted Using Combined Clinical and Genetic Factors in the Perioperative Period of Kidney Transplantation and Associated with Acute Rejection
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AG + GG is associated with decreased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype AA.
Notes: alleles complemented to plus chromosomal strand.
Article: Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
Gene: OPRM1
Variant/haplotype: rs642489
Drug(s): ethanol
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to ethanol as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand. No significant association between this variant and any individual item or total score on the Subjective High Assessment Scale-Expectations (SHAS-E) questionnaire.
Article: HLA-DQA1*05 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn’s disease
Variant/haplotype: rs2097432
Drug(s): infliximab
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with decreased response to infliximab in people with Crohn Disease as compared to genotype TT.
Notes: "Furthermore, HLA-DQA1*05 G carriage was significantly associated with an elevated risk of loss response to IFX treatment (adjusted HR = 2.55, 95% CI 1.78–3.68, P < 0.001; Figure 3B and Supplementary Table 2)." Authors describe locus as HLADQ A1*05A>G (rs2097432). Alleles complemented
Article: Efficacy and Safety Profile of Z-215 (Azeloprazole Sodium), a Proton Pump Inhibitor, Compared with Rabeprazole Sodium in Patients with Reflux Esophagitis: A Phase II, Multicenter, Randomized, Double-Blind, Comparative Study
Gene: CYP2C19
Variant/haplotype: CYP2C19*1
Drug(s): rabeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *1/*1 is not associated with response to rabeprazole in people with Gastroesophageal Reflux as compared to CYP2C19 *1/*1.
Notes: as compared to patients with the *1/*2 or *1/*3 genotype, or those with the *2/*2, *2/*3 or *3/*3 genotype. To assess the effects of CYP2C19 genotype, the endoscopic healing rate was assessed by the investigator at Week 8 according to CYP2C19 genotype (homozygous EM and heterozygous EM and PM). The endoscopic healing rate was not dependent on CYP2C19 genotype in any group (10 mg Z-215: 125 patients, 20 mg Z-215: 126 patients, 40 mg Z-215: 126 patients, and 10 mg rabeprazole: 126 patients). Please note that the authors did not specify whether every one of these genotypes was present in the population, only that they genotyped for them.
Article: SLCO1B1 genetic variation and hormone therapy in menopausal women
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): conjugated estrogens
Phenotype category: Efficacy
Significant: yes
Association: Genotype CT is associated with increased response to conjugated estrogens in women with Menopause as compared to genotype TT.
Notes: Women with the CT genotype had a significantly increased reduction in night sweats following hormonal therapy than women with the TT genotype.
Article: Pharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): clopidogrel
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C19 *2/*2 + *2/*3 is associated with decreased metabolism of clopidogrel in healthy individuals as compared to CYP2C19 *1/*1.
Notes: PMs and IMs had lower con-centrations of active metabolite than did *1/*1 and PMs had lower concentrations than did IMs. CYP2C19 *2/*3 is associated with increased area under the plasma concentration-time curve and Cmax as compared to CYP2C19 *1/*1.; Note: P values were NOT provided in the study. Authors chose to report of confidence interval cut-off of 90%, (not classical cut-off of 95%). Confidence interval of 90% does not cross 1 so that suggesting significance.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Gene: CYP1A2
Variant/haplotype: rs2069526
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele T.
Article: Lower Calcineurin Inhibitor Doses in Older Compared to Younger Kidney Transplant Recipients Yield Similar Troughs
Gene: CYP3A5
Variant/haplotype: CYP3A5*1
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1 is associated with decreased trough concentration of tacrolimus in people with Kidney Transplantation.
Notes: During first 6 months post-transplant.
Article: Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients
Gene: UMPS
Variant/haplotype: rs2291078
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with decreased response to capecitabine and fluorouracil in people with Neoplasm Metastasis as compared to allele T.
Notes: pfSNP identified 2800 SNPS associated with key-words: 5-FU, capecitabine and oxilaplatin and colorectal cancer. Various criteria were used to determine 1536 SNPs to genotype. These SNPs were genotyped in a discovery cohort (N=62) and tested in a validation cohort (N=27). Both cohorts consisted of patients with colorectal cancer metastasis in liver. 36 SNPs were initially significantly associated with drug response but only 3 remained significant in the validation cohort (before Bonferroni correction): rs2291078 A, rs3772809 G, rs3772810 G. All three SNPs were in perfect LD, and were initially associated with the non-responder phenotype, but the association did not remain significant after Bonferroni correction.
Article: In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizers
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 poor metabolizer is associated with decreased concentrations of endoxifen in women Breast Neoplasms as compared to CYP2D6 normal metabolizer.
Notes: The patients of the cohort (83% White, 15% Black) were genotype with AmpliChip CYP450 test. The variations used to define the star alleles are not reported. The diplotypes of the patients are not reported. The alleles found in the cohort are not explicit reported but graphic 3 shows *1, *2, *35, *9, *10, *17, *29, and *41. The study included UMs and PM but no CYP2D6 star allele is reported for those phenotypes. *1, *2, *35 are grouped as active alleles and any combination of these defines the extensive metabolizer. *9, *10, *17, *29, and *41 are grouped as reduced function alleles. The article subgroups the IMs into EM/IM, EM/PM, IM/IM, IM/PM.
Article: Individualized Angiotensin‐Converting Enzyme (ACE)‐Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model
Gene: BDKRB1
Variant/haplotype: rs12050217
Drug(s): perindopril
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with decreased response to perindopril in people with Coronary Artery Disease as compared to genotype GG.
Notes: Three SNPS are combined for a risk score ranging between 0 and 6: rs275651, rs5182, and rs12050217. Patients with risk scores of 0 and 1 and treated with perindopril had absolute risk reductions of 7.50% (95% CI: 3.69-11.73) and 4.30% (95% CI: 2.00-6.53), respectively. Nonsignificant estimated absolute risk increase of 1.32% was observed in patients with a PGXscore >=3. Lower risk score had better response to treatment by primary endpoint of cardiovascular mortality, nonfatal MI, and resuscitated cardiac arrest. Part of PERGENE trial for cardiovascular outcomes.
Article: GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis
Gene: GRIK4
Variant/haplotype: rs1954787
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to antidepressants in people with Depressive Disorder, Major as compared to allele T.
Notes: Meta-analysis combining 5 studies.
Article: Clinical significance of UGT1A1 gene polymorphisms on irinotecan-based regimens as the treatment in metastatic colorectal cancer
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): FOLFIRI, irinotecan
Phenotype category: Efficacy
Significant: no
Association: UGT1A1 *28 is not associated with increased response to FOLFIRI or irinotecan in people with Colorectal Neoplasms as compared to UGT1A1 *1.
Notes: Response rates were complete and partial response (CR + PR), or complete and partial response and stable disease (CR + PR + SD). No significant differences between any of the genotypes ((TA)6/(TA)6, (TA)6/(TA)7, (TA)7/(TA)7) were seen for either type of response rate.
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: KCNQ1
Variant/haplotype: rs163184
Drug(s): sitagliptin
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to sitagliptin in people with Diabetes Mellitus, Type 2.
Notes: "KCNQ1 gene polymorphisms also significantly affected treatment outcomes. Patients with the rs163184 GG allele in the study group had a median HbA1c improvement of 0.81 (IQR, 0.62–0.92) compared with 1.16 (IQR, 0.91–1.32) in the control group (P < .001), suggesting lower responsiveness to sitagliptin and better response to gliclazide."