shlokn/autogkb huggingface dataset:
Article: Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease
Gene: APOE
Variant/haplotype: rs429358
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to hmg coa reductase inhibitors in people with Alzheimer Disease as compared to genotypes CT + TT.
Notes: Analysis of 859 subjects with AD (ROS/MAP dataset) and re-analysis of a clinical trial of simvastatin in 171 AD patients (simvastatin trial) found no significant difference in ADAS-cog scores between statin-treated patients and those treated with placebo. However, analysis of separate genotype subgroups found that E4/E4 subjects in the ROS/MAP dataset had significantly better cognitive function over a 10-year follow-up compared to those treated with placebo. Additionally, there was a non-significant trend in the simvastatin trial for subjects with the E4/E4 genotype who were treated with simvastatin to have lower ADAS-cog scores than E4/E4 patients treated with placebo.
Article: Voriconazole Metabolism, Toxicity, and the Effect of Cytochrome P450 2C19 Genotype
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2/*2 (assigned as poor metabolizer phenotype) is associated with increased concentrations of voriconazole as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Article: Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study
Gene: IFNL4
Variant/haplotype: rs11322783
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: yes
Association: Allele TT is associated with increased response to boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin or telaprevir in people with Hepatitis C, Chronic as compared to allele G.
Notes: This variant is in almost complete LD with rs12979860 (r2=0.94) in caucasians. This variant was significantly associated with SVR to triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Gene: CYP3A43
Variant/haplotype: rs472660
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele G.
Article: Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
Gene: GABRA2
Variant/haplotype: rs11503014
Drug(s): propofol
Phenotype category: Other
Significant: yes
Association: Genotype CC is associated with decreased response to propofol as compared to genotypes CG + GG.
Notes: Patients with the CC genotype had significantly smaller decreases (-9.44% +/-6.94%) in heart rate after propofol anesthesia as compared to patients with the CG or GG genotypes (-12.85% +/- 8.54). Please note: the authors examined 58 SNPs but did not do multiple testing corrections.
Article: A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*11
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *11 is associated with decreased clearance of efavirenz in healthy individuals as compared to CYP2B6 *1/*1.
Notes: Subjects homozygous for CYP2B6*11  displayed 20% lower apparent oral clearance as compared to wild type.
Article: Dose-Finding and Pharmacokinetic Study to Optimize the Dosing of Irinotecan According to the UGT1A1 Genotype of Patients With Cancer
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): irinotecan
Phenotype category: Metabolism/PK
Significant: no
Association: UGT1A1 *1/*28 + *28/*28 is not associated with concentrations of irinotecan in people with Neoplasms as compared to UGT1A1 *1/*1.
Notes: No significant difference in dose-adjusted irinotecan area under the plasma concentration-time curve (AUC) was seen between the two genotype groups.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*2xN
Drug(s): methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *1/*2xN + *2/*2xN (assigned as ultrarapid metabolizer phenotype) are associated with increased concentrations of methadone in people with Opioid-Related Disorders as compared to CYP2D6 normal metabolizer.
Notes: CYP2D6 ultrarapid metabolizers had significantly higher doses of (R)-, (S)- and (R,S)-methadone compared to those classed as normal metabolizers. No details about which specific variants/alleles were tested for are given and it is not apparent how different genotypes were categorized into metabolizer phenotypes.
Article: An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3′-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients
Gene: CYP2B6
Variant/haplotype: rs1042389
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is not associated with concentrations of efavirenz in people with HIV Infections as compared to genotypes CC + CT.
Article: Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy
Gene: ABCC2
Variant/haplotype: rs4148386
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG are associated with increased clearance of carbamazepine in people with Epilepsy as compared to genotype GG.
Notes: This association was only significant in the African American patients and not in Caucasian patients. Carbamazepine-10-11 epoxide: carbamazepine ratio was also significantly higher in African American patients with AA+AG vs GG (p=0.049).
Article: The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC
Gene: CES1
Variant/haplotype: rs2244613
Drug(s): dabigatran
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with decreased dose-adjusted trough concentrations of dabigatran in people with Atrial Fibrillation as compared to allele T.
Article: OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): morphine
Phenotype category: Dosage
Significant: yes
Association: Genotype AG is associated with increased dose of morphine in people with Neoplasms as compared to genotype AA.
Notes: The setting was for palliative care of cancer patients.
Article: TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics
Gene: ERICH3
Variant/haplotype: rs696692
Drug(s): serotonin
Phenotype category: Other
Significant: yes
Association: Allele T is associated with decreased concentrations of serotonin in people with Depressive Disorder as compared to allele C.
Notes: in patients taking citalopram or escitalopram. Baseline plasma serotonin concentrations before SSRI therapy, as well as changes in serotonin were used as a biomarker for response to SSRIs and GWAS was done w/respect to changes in plasma serotonin concentration. The T allele was associated with higher baseline plasma serotonin concentrations, as well as greater decreases in plasma serotonin concentrations at 4 and 8 weeks after beginning SSRI therapy.
Article: Contribution of BDNF and DRD2 genetic polymorphisms to continued opioid use in patients receiving methadone treatment for opioid use disorder: an observational study
Gene: BDNF
Variant/haplotype: rs6265
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele C.
Notes: Response to methadone was measured as the number of urine screens which were positive for opioids during methadone treatment.; Please note that alleles have been complemented to the positive strand.
Article: Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis
Gene: XRCC1
Variant/haplotype: rs25487
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT are associated with increased response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotype TT.
Notes: "Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001)."
Article: Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is associated with increased response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes AA + AC.
Notes: Patients with the CC genotype had better response to platinum based chemotherapy than patients with other genotypes.
Article: Polymorphism of Drug Transporters, Rather Than Metabolizing Enzymes, Conditions the Pharmacokinetics of Rasagiline
Gene: SLC22A1
Variant/haplotype: rs12208357
Drug(s): rasagiline
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with decreased clearance of rasagiline in healthy individuals as compared to genotype CC.
Notes: and lower tmax remained significant after Bonferroni. Subjects with the *1/*3 (or rs12208357 C/T) genotype for SLC22A1 showed lower tmax than subjects with the *1/*1 (or rs12208357 C/C) genotype
Article: Pharmacogenetic markers of CYP2B6 associated with efavirenz plasma concentrations in HIV-1 infected Thai adults
Gene: CYP2B6
Variant/haplotype: rs8192709
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with concentrations of efavirenz in people with HIV Infections as compared to genotype CC.
Article: CFTR modulators response of S737F and T465N CFTR variants on patient-derived rectal organoids
Gene: CFTR
Variant/haplotype: rs758900656
Drug(s): elexacaftor / tezacaftor / ivacaftor
Phenotype category: PD
Significant: not stated
Association: Allele A is associated with increased clinical benefit to elexacaftor / tezacaftor / ivacaftor.
Notes: We then investigated the response to CFTR modulators of the rare and uncharacterized variant T465N using rectal organoids derived from a CF patient carrying the T465N/Q39X genotype."Ivacaftor (VX-770) alone could not potentiate the T465N/Q39X-CFTR function as registered in both assays. The use of single correctors such as lumacaftor (VX-809) and tezacaftor (VX-661) also contributed minimally to the channel restoration with no difference in organoid swelling rates or anion secretion."ETI triple therapy increased CFTR-T465N processing and trafficking significantly, enhancing anion transport and FIS rates in vitro."the theratyping of the very rare T465N variant present in trans with a null allele in patient-derived organoids predicted potential clinical benefits of ETI treatment for patients with this variant.
Article: Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*4
Drug(s): citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
Phenotype category: Dosage, Efficacy
Significant: yes
Association: CYP2D6 *4/*4 is associated with decreased dose of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine or sertraline 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.) SSRIs were grouped together for this analysis (32.5 % of patients were taking paroxetine; 13.4% fluvoxamine;11.6% fluoxetine; 7.3% sertraline;4.6% citalopram;0.1% escitalopram.  Mean SSRI dose was significantly lower at the 3rd  prescription (difference 0.17 DDD) but not significant for the following prescriptions.   Genotypes were not in Hardy-Weinberg equilibrium; frequency below is for a larger population that included patients treated with other antidepressants.
Article: Thiopurine metabolites variations during co-treatment with aminosalicylates for inflammatory bowel disease: Effect of N-acetyl transferase polymorphisms
Gene: NAT1
Variant/haplotype: NAT1*3, NAT1*4, NAT1*10
Drug(s): mesalazine, thioguanine
Phenotype category: Metabolism/PK
Significant: yes
Association: NAT1 *10 is associated with decreased concentrations of mesalazine and thioguanine in children with Colitis, Ulcerative, Crohn Disease and Inflammatory Bowel Diseases as compared to NAT1 *4 + *3.
Notes: Genotyping based on two SNPs: rs1057126 (T1088A) and rs15561 (C1095A). Analysis compared slow acetylators versus rapid acetylators.
Article: Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin’s lymphoma being treated for invasive pulmonary aspergillosis
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C19 *1/*2 (assigned as intermediate metabolizer phenotype) is associated with decreased exposure to voriconazole in men with Lymphoma, Non-Hodgkin.
Notes: in a patient when co-administered with dexamethasone. "To our knowledge, this is the first report of a dose-dependent interaction between voriconazole and dexamethasone in the patient carrying the CYP2C19*1*2 genotype (IM). "
Article: Pharmacogenetics of Interaction between Depot Medroxyprogesterone Acetate and Efavirenz, Rifampicin and Isoniazid during Treatment of HIV and Tuberculosis
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): medroxyprogesterone
Phenotype category: Metabolism/PK
Significant: no
Association: NAT2 slow acetylator is not associated with metabolism of medroxyprogesterone in women with HIV Infections and Tuberculosis as compared to NAT2 rapid acetylator.
Notes: No significant associations between NAT2 acetylator status and any primary pharmacokinetic parameter for medroxyprogesterone acetate. Patients also receiving efavirenz-based ART and rifampicin plus isoniazid for treatment. NAT2 genotypes were categorized based on combinations of rs1801280 (NAT2*5), rs1799930 (NAT2*6), rs1799931 (NAT2*7), and rs1801279 (NAT2*14), as slow if homozygous for the variant allele at any locus (i.e. AA, CC, AA, and AA, respectively), or heterozygous at 2 or more loci; intermediate if heterozygous at a single locus; or extensive if no variant allele at any locus. 5(11%) were NAT2 rapid acetylators, 20(45%) were NAT2 intermediate acetylators, and 19(43%) were NAT2 slow acetylators.
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Variant/haplotype: rs7247267
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele G.
Notes: There was a trend but significance was not attained. Observations: 2.81mm Hg decreased reduction of diastolic blood pressure per T allele in PEAR + GERA, 0.07 mm Hg decreased reduction of diastolic blood pressure per T allele in NORDIL, and 1.40 mm Hg decreased reduction of diastolic blood pressure per T allele in PEAR + GERA + NORDIL.
Article: DPYD Variants as Predictors of 5-fluorouracil Toxicity in Adjuvant Colon Cancer Treatment (NCCTG N0147)
Gene: DPYD
Variant/haplotype: rs67376798
Drug(s): fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotype AT is not associated with response to fluorouracil in people with Colonic Neoplasms as compared to genotype TT.
Notes: The A allele was not associated with disease-free survival time.
Article: Relationship of CYP3A5 genotype and ABCB1 diplotype to tacrolimus disposition in Brazilian kidney transplant patients
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of tacrolimus in people with Kidney Transplantation.
Notes: 3 - 12 months post-transplant. In multivariate linear regression analysis, the AAA/AAA haplotype (rs1045642, rs1128503, rs2032582) showed a significant effect on dose-adjusted trough concentrations (C0/D) of tacrolimus (those with the AAA/AAA haplotype have increased C0/D compared to those with non-AAA/AAA haplotypes). In chi-squared analyses, no significant association was seen for trough concentrations or dose. Please note alleles have been complemented to the plus chromosomal strand.
Article: Rapid and ultra-rapid metabolizers with CYP2C19*17 polymorphism do not respond to standard therapy with proton pump inhibitors
Gene: CYP2C19
Variant/haplotype: CYP2C19*2, CYP2C19*3, CYP2C19*17
Drug(s): esomeprazole, pantoprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *17/*17 is associated with increased clearance of esomeprazole and pantoprazole in healthy individuals as compared to CYP2C19 *2/*3.
Notes: Blood samples were collected to determine plasma concentration at 0, 1, 3, 4, 6, and 24 hours after the dose on the first and last day of administration
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with increased dose of warfarin in people with heart valve replacement as compared to allele C.
Notes: Samples, genotypes and INRs from a cohort of 551 patients were used to derive an algorithm which was used to predict daily warfarin maintenance dose in a second cohort of 236 patients. Note: the authors state that "SNPs were tested for deviations from HWE using the chi-squared test, and for their association with the warfarin dose by Spearman correlation analysis using a *co-dominant* model." rs1057910 remained significantly associated with warfarin maintenance dose in the multivariate analysis.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: SLC47A1
Variant/haplotype: rs2120274
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.
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 rs2120274 as top SNP for SLC47A1
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Gene: ERCC6L2
Variant/haplotype: rs689979
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele C.
Notes: Significance was not attained. Observations: 2.68 mm Hg decreased reduction of systolic blood pressure per T allele in PEAR + GERA, 0.26 mm Hg increased reduction of systolic blood pressure per T allele in NORDIL, and 1.84 mm Hg decreased reduction of systolic blood pressure per T allele in PEAR + GERA + NORDIL.
Article: Genetic polymorphisms of microsomal epoxide hydrolase and UDP-glucuronosyltransferase (UGT) and its effects on plasma carbamazepine levels and metabolic ratio in persons with epilepsy of South India: A cross-sectional genetic association study
Gene: UGT2B7
Variant/haplotype: rs7439366
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype TT is associated with increased dose-adjusted trough concentrations of carbamazepine in people with Epilepsy as compared to genotypes CC + CT.
Notes: "In UGT2B7*2, PWE carrying homozygous mutant genotype (TT) had higher levels when compared with CT (3.09 μg/mL vs. 2.74 μg/mL) (conversion of the natural logarithm of plasma CBZ to plasma CBZ level using e^lnplasma CBZ level) and found no statistical significance between the above UGT2B7 genotypes and plasma CBZ levels"
Article: Effect of UGT2B10, UGT2B17, FMO3, and OCT2 Genetic Variation on Nicotine and Cotinine Pharmacokinetics and Smoking in African Americans
Gene: UGT2B10
Variant/haplotype: rs2942857
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with increased exposure to nicotine in people with Tobacco Use Disorder as compared to genotypes AA + AC.
Notes: This annotation was on rs116294140, but dbSNP has merged these two rs IDs.
Article: Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine
Gene: ITPA
Variant/haplotype: rs7270101
Drug(s): azathioprine, mercaptopurine
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Genotypes AC + CC is associated with increased metabolism of azathioprine or mercaptopurine in people with Inflammatory Bowel Diseases or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.
Notes: as measured by higher concentrations of 6-TGNs in RBCs.
Article: Effects of NT5C2 germline variants on 6-mecaptopurine metabolism in children with acute lymphoblastic leukemia
Gene: NT5C2
Variant/haplotype: rs72846714
Drug(s): mercaptopurine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG are associated with decreased metabolism of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype GG.
Notes: This variant is associated with a significant decrease in TGN metabolite levels during 6-MP treatment in Children With Acute Lymphoblastic Leukemia. The study showed that rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in-cis.
Article: Genetic Variants Influencing Plasma Renin Activity in Hypertensive Patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: TXNDC11
Variant/haplotype: rs3784921
Drug(s): hydrochlorothiazide
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of hydrochlorothiazide in people with Hypertension as compared to allele T.
Article: Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects
Gene: SLCO1B1
Variant/haplotype: SLCO1B1*1, SLCO1B1*15
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: SLCO1B1 *15 is associated with increased concentrations of atorvastatin in healthy individuals as compared to SLCO1B1 *1/*1.
Notes: Note *17 was listed in the original publication. *17 was merged with *15 due to PharmVar 2021 update.