shlokn/autogkb huggingface dataset:
Article: Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate
Gene: GRIN2B
Variant/haplotype: rs2058878
Drug(s): acamprosate
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to acamprosate in people with Alcoholism as compared to allele T.
Notes: Tag SNPs (518 total) were selected within genes associated with alcoholism as well as genes encoding enzymes involved in glycine metabolism, glycine transporters, subunits of glycine receptors, NMDA receptors, genes involved in glutamate reuptake, synthesis or degradation and genes with reported associations with acamprosate treatment outcomes in human or animal studies. The length of time to first alcohol use “survival analysis method” was used to examine associations between clinical variables and genetic markers with efficacy of acomprasate (its ability to length  the duration of abstinence from alcohol).  The analyses were replicated in a subset of 110 participants from PREDICT, a double-blind randomized controlled trial that compared treatment outcomes including length of abstinence among alcohol- dependent subjects of German descent recruited from inpatient facilities and treated with acamprosate, naltrexone or placebo for 3 months. The strongest association finding, was for the A allele at  rs2058878 A allele, which remained significantly associated with longer abstinence even after Bonferroni correction for the number of SNPs included in the analyses (P = 4.6 × 10 - 5, corrected P = 0.024).
Article: Genetic Variation (CHRNA5), Medication (Combination Nicotine Replacement Therapy vs. Varenicline) and Smoking Cessation
Gene: CHRNA3, CHRNA5
Variant/haplotype: rs16969968
Drug(s): nicotine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to nicotine in people with Tobacco Use Disorder as compared to genotype GG.
Notes: Participants with the AA or AG genotypes were significantly more likely to respond to nicotine replacement therapy (NRT) than participants with the GG genotype.
Article: Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): Proton pump inhibitors
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AC is associated with increased response to Proton pump inhibitors in people with eosinophilic esophagitis as compared to genotypes CC + CT.
Notes: as measured by PEC Reduction and EREFS Score Reduction. Alleles complemented (triallelic snp). "Patients with the STAT6 rs12368672 C/C genotype showed a lower reduction in EREFS score compared to patients with G/C + G/G genotypes (p = 0.011) (Table 5). Furthermore, a higher EREFS score reduction was observed in individuals with ABCB1 rs2032582 T/T+T/G genotypes compared to those with A/A+G/A+G/G genotypes (p = 0.045) (Table 5); none of these differences reached the threshold for statistical significance after the Bonferroni correction for multiple comparisons "
Article: S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis
Gene: UGT1A1
Variant/haplotype: UGT1A1*60
Drug(s): irinotecan, oxaliplatin, tegafur / gimeracil / oteracil
Phenotype category: Efficacy
Significant: yes
Association: UGT1A1 *60 is associated with decreased response to irinotecan, oxaliplatin and s 1 (combination) in people with Colorectal Neoplasms.
Notes: Those with the *60 allele had a lower objective response rate (52% responders) as compared to those without the * 60 allele (90% responders).
Article: Evaluating Predictive Pharmacogenetic Signatures of Adverse Events in Colorectal Cancer Patients Treated with Fluoropyrimidines
Gene: DPYD
Variant/haplotype: rs75017182
Drug(s): capecitabine, fluorouracil
Phenotype category: Dosage
Significant: yes
Association: Genotype CG is associated with dose of capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype GG.
Notes: Clinical data about adverse events were collected from patient records and laboratory charts for 12 weeks after the initiation of therapy. Delays or reductions in the administration of 5'FU or capecitabine due to adverse events were recorded as primary outcomes, and grade 3,4,5 adverse events were analyzed as secondary outcomes. "Dose" here refers to dose modification.; Note: the reported parameters for this SNP are really for a haplotype (the authors refer to it as a "signature") that includes any minor alleles for the following SNPs:  rs3918290 (T), rs67376798 (A), rs75017182(C), rs56038477 (T).
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Variant/haplotype: rs8023369
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 G.
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: Association between CXCL10 and DPP4 Gene Polymorphisms and a Complementary Role for Unfavorable IL28B Genotype in Prediction of Treatment Response in Thai Patients with Chronic Hepatitis C Virus Infection
Gene: DPP4
Variant/haplotype: rs17848916
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b
Phenotype category: Efficacy
Significant: no
Association: Genotype AC is not associated with response to peginterferon alfa-2a or peginterferon alfa-2b in people with Hepatitis C, Chronic as compared to genotype AA.
Notes: PEG-interferon alfa (2a and b) was co-adminstered with ribavirin. Response was assessed by sustained virological response (SVR) percent by genotype. Please note, alleles have been complemented to the + chromosomal strand.
Article: A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism
Variant/haplotype: rs12461964
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased clearance of nicotine as compared to allele G.
Notes: The minor allele was independently associated with decreased NMR, indicating decreased rate of nicotine clearance. rs56113850 and rs12461964 were in LD with CYP2A6*2, and esv2663194 (not annotated) was in LD with CYP2A6*9. rs56113850, rs12461964, and esv2663194 emerged as signals independently associated with NMR in GWAS and in conditional analyses. A fourth signal, rs113288603, was not significant in GWAS, but was significant after conditioning on the top associated SNP, rs56113850.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRK1
Variant/haplotype: rs6985606
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele C.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy. Please note that alleles have been complemented to the positive strand.
Article: Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to efavirenz in people with HIV Infections and Tuberculosis as compared to genotypes GG + GT.
Notes: No significant difference in median CD4 T cell counts of each genotype at different time points was seen in efavirenz group (p = 0.818, 0.838, 0.783, 0.753 and 0.587 for baseline, weeks 12, 24, 36 and 48 of ART, respectively).
Article: Effects of GRK5 and ADRB1 polymorphisms influence on systolic heart failure
Gene: GRK5
Variant/haplotype: rs2230345
Drug(s): Beta Blocking Agents
Phenotype category: Efficacy
Significant: not stated
Association: Genotype AT is not associated with response to Beta Blocking Agents in people with Heart Failure as compared to genotype AA.
Article: Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy
Gene: ABCB1
Variant/haplotype: rs1128503
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.
Article: Effects of CYP3A5 polymorphism on the pharmacokinetics of a once-daily modified-release tacrolimus formulation and acute kidney injury in hematopoietic stem cell transplantation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with decreased trough concentration of tacrolimus in people with hematopoietic stem cell transplantation as compared to CYP3A5 *3/*3.
Notes: Patients were started on tacrolimus continuous infusion and then converted to once-daily oral intake. Intravenous infusion of micafungin was given during the neutropenic phase, then seven days after switching from tacrolimus continuous infusion to once-daily oral intake, antifungal agents were switched from intravenous micafungin to oral azole antifungal agents. Whole blood samples from the patients were collected 4-7 days after switching to once-daily tacrolimus oral dosing and then 4-7 days after switching from intravenous micafungin to oral azole antifungals. When patients were also taking azole antifungal agents, there was a significant difference in trough concentrations. When patients were NOT taking azole antifungal agents, there was no significant difference in trough concentrations (p=0.053).
Article: SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*3 + *3/*3 are associated with decreased concentrations of atorvastatin in healthy individuals as compared to CYP3A5 *1/*1.
Notes: CYP3A5 *1/*3 and *3/*3 genotypes were associated with lower AUC/DW, Cmax/DW and tmax and to higher Cl/F compared to the *1/*1 genotype.
Article: Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study
Gene: NR1I3
Variant/haplotype: rs2307424
Drug(s): (R)-methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with increased clearance of (R)-methadone in people with HIV Infections.
Notes: "Being HIV+, taking ART, presence of the rare ABCB1 rs2032582 T allele, and combined presence of the NR1I3 rs2307424 GG and rs3003596 GG genotypes if taking EFV each significantly increased R-methadone CL/F."
Article: Evaluation of genetic association of neurodevelopment and neuroimmunological genes with antipsychotic treatment response in schizophrenia in Indian populations
Gene: CCL2
Variant/haplotype: rs4586
Drug(s): antipsychotics
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to antipsychotics in people with Schizophrenia as compared to allele C.
Notes: In low severity schizophrenia patient subgroup
Article: Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction
Gene: BDNF
Variant/haplotype: rs10835210
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Genotype CC is associated with increased dose of methadone in people with Heroin Dependence as compared to genotypes AA + AC.
Notes: This association was statistically significant after permutation analysis based on 40,000 replicates, but not statistically significant after adjusting for testing for multiple SNPs (Bonferroni correction). Note; this SNP was in LD with rs7934165 (r^2>0.7) and not independent.
Article: S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer
Gene: CYP19A1
Variant/haplotype: rs4646
Drug(s): tamoxifen
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AC are associated with increased response to tamoxifen in women with Breast Neoplasms as compared to genotype CC.
Notes: Women were on tamoxifen (n=250) or on unnamed aromatase inhibitors (n=37). Disease free survival was compared at 62.7 weeks and 55.6 weeks follow-up for all women for all women, though different week comparisons were used for each significant association that was found. This association was significant in all women combined and the pre-menopausal subset, but not the post-menopausal subset. The AA genotype was associated with poorer disease free survival in post-menopausal women (p=0.005).
Article: Genome-Wide Association Analysis in Asthma Subjects Identifies SPATS2L as a Novel Bronchodilator Response Gene
Gene: SPATS2L
Variant/haplotype: rs295137
Drug(s): salbutamol
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to salbutamol in people with Asthma as compared to allele C.
Notes: These were two attempts to replicate the association (which did not reach significance) noted in the combined group from 6 clinical trials.
Article: Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of warfarin as compared to allele C.
Notes: There were no significant differences in mean warfarin stable dose (mg/week) (+3 INR stable, no dose change) in the overall group or in the identified "white" subgroup. The self-identified "non-white" subgroup had slight differences in mean warfarin doses (ANOVA p= 0.048 CC = 29.2, CT = 33.1, TT = 33.0). Two self-reported "non-white" patients had the TT genotype.
Article: Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): clopidogrel
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2 (assigned as poor metabolizer phenotype) is associated with increased dose of clopidogrel in healthy individuals as compared to CYP2C19 *1 (assigned as normal metabolizer phenotype) .
Notes: Assays done in blood samples of six each of *1/*1 (EM),*1/*2(IM) and *2/*2(PM) [based on only assaying for *2; 2 EMs were *1/*17 and one IM was a *2/*17] were compared for MPA4 (maximal platelet aggregation 4 hrs post-dose) and for active metabolite area under the curve. For the EMs, this result was significant for both the 150 and 300 mg/day doses; for the IMs and PMs, it was significant for the 300 mg/day dose.  At day 8, PMs needed 300 mg/day and IMs needed 150 mg/day to attain a similar MPA4 as EMs on the 75 mg/day dose.
Article: Genetic polymorphisms in the long noncoding RNA MIR2052HG offer a pharmacogenomic basis for the response of breast cancer patients to aromatase inhibitor therapy
Variant/haplotype: rs13260300
Drug(s): anastrozole, exemestane
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with increased response to anastrozole and exemestane in women with Breast Neoplasms as compared to allele C.
Notes: Patients included postmenopausal women with resected stage I–III breast cancer that was ERa and/or PgR positive and randomized to five years of anastrozole or exemestane.
Article: Prolonged Toxicity after Amitriptyline Overdose in a Patient Deficient in CYP2D6 Activity
Gene: CYP2D6
Variant/haplotype: CYP2D6*4
Drug(s): amitriptyline
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *4/*4 is associated with increased concentrations of amitriptyline.
Notes: Intentionally overdosed on amitriptyline. Subject (found comatose) displayed prolonged rising of serum total amitriptyline and nortriptyline concentrations for at least 6 days after admission.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: TBL1XR1
Variant/haplotype: rs57449396
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to allopurinol as compared to allele C.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: Genetic Variants Associated With Uncontrolled Blood Pressure on Thiazide Diuretic/β‐Blocker Combination Therapy in the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) and INVEST (International Verapamil‐SR Trandolapril Study) Trials
Variant/haplotype: rs35123024
Drug(s): atenolol, hydrochlorothiazide
Phenotype category: Efficacy
Significant: not stated
Association: Allele C is associated with decreased response to atenolol and hydrochlorothiazide in people with Hypertension as compared to allele T.
Notes: Variant located near OR5H14. C allele associated with increased odds of uncontrolled blood pressure following thiazide diuretic/beta-blocker combination therapy. Variant only reached suggestive significance in discovery GWAS. Consistent direction of association found across discovery and replication cohorts but did not reach genome-wide significance in meta-analysis of all cohorts.
Article: Characterisation of the Clinical Pharmacokinetics of Actinomycin D and the Influence of ABCB1 Pharmacogenetic Variation on Actinomycin D Disposition in Children with Cancer
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): dactinomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of dactinomycin in children with Neoplasms as compared to allele G.
Notes: No significant difference in actinomycin D clearance was seen between the genotypes (AA, AG, GG). Please note that alleles have been complemented to the plus chromosomal strand.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: TH
Variant/haplotype: rs6356
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of methadone in people with Heroin Dependence as compared to allele C.
Article: CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of trough lacosamide concentration or clinical response
Gene: ABCC2
Variant/haplotype: rs717620
Drug(s): lacosamide
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased exposure to lacosamide in children with Epilepsy as compared to allele C.
Notes: "Additionally, the presence of the rs717620 (C > T) variant, located in ABCC2, was significantly associated with lower exposure levels in monotherapy (β = −0.305, p = 0.048; Table 2)."
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DBH
Variant/haplotype: rs129882
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of methadone in people with Heroin Dependence as compared to allele C.
Article: Impact of the CYP2C8 *3 polymorphism on the drug–drug interaction between gemfibrozil and pioglitazone
Gene: CYP2C8
Variant/haplotype: CYP2C8*1, CYP2C8*3
Drug(s): pioglitazone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C8 *1/*1 is not associated with metabolism of pioglitazone in healthy individuals as compared to CYP2C8 *1/*3 + *3/*3.
Notes: Specifically, *1/*1 is not associated with t1/2 (half-life) of pioglitazone as compared to *1/*3 + *3/*3.
Article: Association between rs2275913 single‐nucleotide polymorphism of the interleukin‐17A gene and perioperative analgesic use in cosmetic orthognathic surgery
Gene: IL17A
Variant/haplotype: rs2275913
Drug(s): opioids
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele A is associated with increased dose of opioids in people with Pain, Postoperative as compared to allele G.
Notes: Opioid dose requirements increased as the copy number of the A allele increased.
Article: The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia
Gene: MYLIP
Variant/haplotype: rs9370867
Drug(s): atorvastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to atorvastatin in people with Hypercholesterolemia as compared to genotypes AG + GG.
Notes: Patients with with heterozygous familial hypercholesterolemia were treated with atorvastatin with the addition of ezetimibe in over half the patients. Patients carrying the AA genotype were more likely to achieve LDL-C levels of less than 130¿mg/dl after 1 year of treatment (75.0%) compared with patients with the GG and GA genotypes (34.5 and 34.8%, respectively; P=0.001). AA genotype had a greater LDL-C response compared with GG genotype. The presence of the G allele was associated with a greater odds of not achieving the LDL-C target in; a multivariate model (OR = 2.08 per G allele, 95% confidence interval (CI) = 1.11-; 3.90, P=0.02).
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: TRIB2
Variant/haplotype: rs10193126
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to allopurinol as compared to allele T.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy
Gene: PTPN22
Variant/haplotype: rs2476601
Drug(s): Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with decreased response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to allele G.
Notes: using either the absolute change in DAS28 or the proportion of good responders and non-responders as outcomes.
Article: SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): atorvastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG is associated with increased response to atorvastatin in people with Hypercholesterolemia as compared to genotype AA.
Notes: Patients with the AG and GG genotype had a greater percent increase in high-density lipoprotein cholesterol (HDL-C) levels as compared to those with the AA genotype. However, no significant differences in percent changes between genotypes were seen for total cholesterol (p=0.81), low density lipoprotein cholesterol (LDL-C; p=0.27) or triglycerides (p=0.30). Patients were treated with atorvastatin for 4 weeks at 10 mg/day.