shlokn/autogkb huggingface dataset:
Article: CYP2B6*6 allele and age substantially reduce steady-state ketamine clearance in chronic pain patients: impact on adverse effects
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): ketamine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *6 is associated with decreased clearance of ketamine in people with Neoplasms and Pain as compared to CYP2B6 *1.
Notes: Median plasma clearance in the *6/*6 genotype was 21.6 L/h, *1/*6 genotype 40.6 L/h and *1/*1 genotype 68.1 L/h. In linear regression analysis the *6 allele explained 40%, 43%, and 41% of the variability in ketamine clearance when the dose was 100, 300 and 500 mg/24 hrs. The authors state that the study was insufficiently powered to study the association between adverse effects and genotype and most of the adverse events were reported in patients with the CYP2B6 *1/*1 genotype.
Article: Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): (R)-methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of (R)-methadone in people with HIV Infections as compared to genotypes AT + TT.
Notes: "The ABCB1 rs2032582 AA genotype significantly decreased R-methadone CL/F."
Article: Influence of CYP2C9 Genotype on warfarin dose among African American and European Americans
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*5, CYP2C9*6, CYP2C9*10, CYP2C9*11
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *11 + *2 + *3 + *5 + *6 is associated with decreased dose of warfarin as compared to CYP2C9 *1.
Notes: Where (*2+*3+*5+*6+*11) are considered variant (*V), Average Daily maintenance dose for *1/*1 > *1/*V > *V/*V.  *5,*6,*11 were only seen in African-Americans.  This result was significant in European-Americans but not in African-Americans.
Article: Convergent animal and human evidence suggests the activin/inhibin pathway to be involved in antidepressant response
Gene: TGFBR3
Variant/haplotype: rs12082710
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased response to antidepressants in people with Depression as compared to genotypes CC + CT.
Notes: Homozygote carriers of the T allele were more frequent among responders to antidepressant treatment as compared to non-responders. Response to treatment was defined as a score reduction of greater than 50% on the 21-item Hamilton Depression Rating Scale (HAM-D) between score at admission and score 5 weeks after treatment initiation.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: TRPV1
Variant/haplotype: rs222749
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to botulinum toxin type a in women with Migraine NOS as compared to allele G.
Notes: The A allele was found at a significantly higher frequency in non-responders than in responders. Note that this variant was not present at Hardy-Weinberg equilibrium in the study cohort (p=0.00006).
Article: A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation
Gene: CYP2C9
Variant/haplotype: CYP2C9*2, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: CYP2C9 *2 + *3 are associated with dose of warfarin.
Notes: This study assessed whether a pharmacogenetic algorithm, which included these variants as well as the VKORC1 rs9923231 and CYP4F2*3 variants, is superior in overall anticoagulation control when compared to clinical standard of care.
Article: Genetic Variation in CYP2D6, UGT1A4, SLC6A2 and SLCO1B1 Alters the Pharmacokinetics and Safety of Mirabegron
Gene: UGT1A4
Variant/haplotype: rs2011425
Drug(s): mirabegron
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GT is associated with increased half-life time of mirabegron in healthy individuals as compared to genotype TT.
Notes: "Also, the t1/2 was higher in the UGT1A4 rs2011425 T/G genotype compared to the T/T genotype (puv = 0.002, pmv = 0.003, β = 0.268, R2 = 0.381) (Table 4). "
Article: Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks
Gene: IL1A
Variant/haplotype: rs1800587
Drug(s): aspirin, diclofenac, ibuprofen, indomethacin, ketorolac, naproxen
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with clinical benefit to aspirin, diclofenac, ibuprofen, indomethacin, ketorolac or naproxen in people with Migraine without Aura as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Influence of common and rare genetic variation on warfarin dose among African–Americans and European–Americans using the exome array
Variant/haplotype: rs12777823
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with dose of warfarin as compared to allele G.
Notes: in patients initiating warfarin treatment with a target international normalized ratio (INR) of 2 to 3. Direction of the relationship of allele to dose is not explicitly stated. rs12777823 is described as "within the CYP2C gene cluster" and "upstream from CYP2C18".
Article: Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population
Gene: VKORC1
Variant/haplotype: rs7294
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin as compared to allele C.
Notes: Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms.
Article: Gemcitabine Metabolic and Transporter Gene Polymorphisms Are Associated with Drug Toxicity and Efficacy in Patients with Locally Advanced Pancreatic Cancer
Gene: RRM1
Variant/haplotype: rs183484
Drug(s): gemcitabine
Phenotype category: Efficacy, Toxicity
Significant: yes
Association: Genotype AC is associated with decreased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AA + CC.
Notes: Patients with the AC genotype had shorter progression free survival than patients with either the AA or the CC genotypes. However, tumor response to therapy and risk of developing neutropenia did not significantly differ between genotype groups. There were four SNPs in this study that, when taken together, affected progression free survival: rs183484, rs2072671, rs760370, and rs9937. Using patients with 0 or 1 variant as reference, patients with 2 variants had an increased HR of 1.79 (P = 0.004) and patients with 3-4 variants has an increased HR of 3.25 (P < 0.001).
Article: Association of variants in NEDD4L with blood pressure response and adverse cardiovascular outcomes in hypertensive patients treated with thiazide diuretics
Gene: NEDD4L
Variant/haplotype: rs75982813
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to atenolol in people with Hypertension as compared to allele G.
Article: CYP2B6 Variants and Plasma Efavirenz Concentrations during Antiretroviral Therapy in Port-au-Prince, Haiti
Gene: CYP2B6
Variant/haplotype: rs36118214
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with decreased metabolism of efavirenz in people with HIV Infections as compared to genotype AA.
Notes: As determined by significantly different efavirenz plasma levels in patients with genotypes in the order AA<AG<GG. Significant after Bonferroni correction for multiple comparisons. This SNP was not in linkage disequilibrium with rs3745274 (516G>T) (r squared = 0.242).
Article: A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism
Gene: CYP2A6
Variant/haplotype: rs56113850
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased clearance of nicotine as compared to allele C.
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: Polymorphism of Drug Transporters, Rather Than Metabolizing Enzymes, Conditions the Pharmacokinetics of Rasagiline
Gene: ABCC2
Variant/haplotype: rs2273697
Drug(s): rasagiline
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of rasagiline in healthy individuals as compared to genotypes AG + GG.
Notes: tmax was significant (other values consistent with this) and remained significant after Bonferroni.
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: EPHX1
Variant/haplotype: rs1051740
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is associated with decreased dose-adjusted trough concentrations of carbamazepine in people with Epilepsy as compared to genotypes CT + TT.
Notes: "In EPHX1 c. 337 (T > C) polymorphism, the PWE carrying CC had lower plasma CBZ levels when compared to the CT genotype (2.45 μg/mL vs. 3.15 μg/mL) (conversion of the natural logarithm of plasma CBZ to plasma CBZ level using e^lnplasma CBZ level), but not found to be statistically significant between EPHX1 genotypes."
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: ABCC8
Variant/haplotype: rs2237991
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele G.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.
Article: KIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment
Gene: KIF6
Variant/haplotype: rs20455
Drug(s): simvastatin
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is associated with decreased response to simvastatin in people with Hypercholesterolemia as compared to genotype AA.
Notes: Please note that alleles have been complemented to the positive strand. A statistically significant association was seen between genotype and change in c-LDL levels, but no association was seen between genotype and change in c-HDL levels.
Article: Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success
Gene: CHRNA5
Variant/haplotype: rs680244
Drug(s): Drugs used in nicotine dependence
Phenotype category: Other
Significant: yes
Association: Allele T is associated with increased response to Drugs used in nicotine dependence in people with Tobacco Use Disorder.
Notes: in haplotype analysis; individuals with haplotype 2 (rs16969968 allele G - rs680244 allele T) were more likely to respond to active treatment/ had a lower risk of relapse (ability to quit smoking as measured by time to relapse to smoking over 60 days) than those with haplotype 2 that were treated with placebo. The ability to quit cigarette smoking was not significantly different in individuals with haplotype 1 (rs16969968 allele G - rs680244 allele C) that underwent active treatment compared to placebo (p=0.36).
Article: Genome-wide association study of patient and clinician rated global impression severity during antipsychotic treatment
Gene: TJP1
Variant/haplotype: rs813676
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to risperidone in people with Schizophrenia as compared to allele C.
Notes: The number of T alleles present in a patient was negatively associated with PGI score. Please note that this variant is in high linkage disequilibrium with rs711355 and rs785423.
Article: Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane–remifentanil following pediatric tonsillectomy
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): remifentanil, sevoflurane
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to remifentanil and sevoflurane in children with tonsillectomy as compared to genotypes AA + AG.
Notes: The GG genotype was not associated with visual analog scale scores, time of induction, respiration recovery, eyeopening, and extubation, Ramsay sedation scores Face, Legs, Activity, Cry, Consolability scale (FLACC) scores.
Article: Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics
Gene: HTR2A
Variant/haplotype: rs6314
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to olanzapine in people with Schizophrenia as compared to genotypes AA + AG.
Notes: The associations were evaluated in conjunction with rs1076560 in the DRD2 gene. rs1076560 GT/rs6314 CC diplotype was associated with better responses to antipsychotics than the rs1076560 GG/rs6314 CT diplotype
Article: A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering
Gene: SUGCT
Variant/haplotype: rs17171676
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with response to hmg coa reductase inhibitors as compared to allele A.
Notes: This SNP was found to be approaching significance in discovery cohort but was not significant in the replication cohort or combined cohorts. Direction of effect and specific allele was not explicitly described in paper.
Article: Effect of SCN1Aand SCN2A gene polymorphisms on the efficacy of valproic acid treatment in Chinese children with epilepsy
Gene: SCN2A
Variant/haplotype: rs17183814
Drug(s): valproic acid
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with increased resistance to valproic acid in children with Epilepsy as compared to genotype GG.
Notes: "However, the situation at the SCN2A rs17183814 locus differs. We observed a significantly higher proportion of individuals with the GG genotype in the VPA responsive group compared to the VPA resistant group (P = 0.025), as depicted in Fig 7. This finding indicates that the GG genotype may be associated with a positive response to VPA treatment. Furthermore, employing the dominant genetic model analysis revealed that the AA+AG genotype was more prevalent in the VPA resistant group than in the responsive group (P = 0.044), further underscoring the potential significance of the rs17183814 locus in predicting VPA treatment outcomes."
Article: Gemcitabine Metabolic and Transporter Gene Polymorphisms Are Associated with Drug Toxicity and Efficacy in Patients with Locally Advanced Pancreatic Cancer
Gene: SLC28A3
Variant/haplotype: rs7853758
Drug(s): gemcitabine
Phenotype category: Efficacy, Toxicity
Significant: no
Association: Genotype GG is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AA + AG.
Notes: Tumor response to therapy, progression free survival, and risk of neutropenia development did not significantly differ between genotype groups.
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP2C9
Variant/haplotype: CYP2C9 poor metabolizer and intermediate metabolizer genotypes
Drug(s): tamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C9 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of tamoxifen in women with Breast Neoplasms.
Article: Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Gene: CYP3A5, ZSCAN25
Variant/haplotype: rs10264272
Drug(s): lumefantrine
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to lumefantrine in women with Malaria and Pregnancy as compared to allele C.
Article: Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma
Variant/haplotype: rs1364805
Drug(s): montelukast
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with increased response to montelukast in people with Asthma as compared to allele G.
Notes: This allele showed a trend toward association but not at the genome wide significance level. Study Cohort: Discovery cohort (N=133): American Lung Association Asthma Clinical Research Center (ALA-ACRC)-supported trials, the Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial (LOCCS) and Effectiveness of Low Dose Theophylline as Add On Therapy for the Treatment of Asthma (LODO) trials. Replication cohort (N=184): Childhood Asthma Research and Education (CARE) Network- Characterizing the Response to a LT Receptor Antagonist and an Inhaled Corticosteroid and Pediatric Asthma Controller Trial (CLIC and PACT).
Article: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
Gene: CHST3
Variant/haplotype: rs730720
Drug(s): docetaxel, thalidomide
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to docetaxel and thalidomide in people with Prostatic Neoplasms as compared to allele T.
Notes: (allele inferred by frequency comparison with dbSNP, actual base not listed in paper, since frequencies are close have low confidence in this allele assignment)
Article: A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis
Gene: TNF
Variant/haplotype: rs1800629
Drug(s): adalimumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to adalimumab in people with Arthritis, Rheumatoid.
Notes: When in a haplotype with rs1799724 and rs361525. Response defined as a 50% percent response to adalimumab therapy according to the American College of Rheumatology criteria (ACR50 responders) at week 12 after treatment initiation. Those homozygous for the GGC (rs361525-rs1800629-rs1799724) haplotype had a significantly lower ACR50 response rate as compared to subjects with any other diplotype (see paper for diplotypes present in population). This effect was more important in a subgroup of patients receiving concomitant methotrexate.
Article: The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with increased metabolism of tacrolimus in children with Kidney Transplantation as compared to genotype CC.
Notes: In pediatric kidney transplantation recipients, CYP3A5 expressers needed higher tacrolimus dose (0.14 mg/kg vs 0.09 mg/kg/12h) than CYP3A5 non-expressers. CYP3A5 expressers also needed more upward dose changes and had lower median tacrolimus concentration and lower C/D ratios. Multivariate analysis showed youger age and CYP3A5 expresser genotype were independently associated with higher tacrolimus dose requirement.
Article: SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours
Gene: CDA
Variant/haplotype: rs1048977
Drug(s): gemcitabine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased metabolism of gemcitabine as compared to genotypes CC + CT.
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. Although this SNP was not significantly associated with gemcitabine clearance, it was significantly associated with clearance of the gemcitabine metabolite dFdU. Pharmacokinetics of dFdU were described by a three-compartment model.; CDA rs1048977 genotype and creatine clearance were significant covariates in the final model to be predict rate of clearance of dFdU, the deaminated metabolite of  gemcitabine.
Article: Association of variants in NEDD4L with blood pressure response and adverse cardiovascular outcomes in hypertensive patients treated with thiazide diuretics
Gene: NEDD4L
Variant/haplotype: rs75982813
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are associated with increased response to hydrochlorothiazide in people with Hypertension as compared to genotype AA.
Notes: If the p for the dominant model (0.0239) is adjusted for 4 SNPs tested, it is 0.092 and the association does not reach significance.  Blood pressure reduction for the heterozygote (AG) is less than for either of the homozygotes for both systolic and diastolic blood pressure.
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: CYP3A5
Variant/haplotype: rs776746
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with concentrations of efavirenz in people with HIV Infections as compared to genotypes CT + TT.
Notes: Alleles given as G and A
Article: Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment
Gene: LDLR
Variant/haplotype: rs688
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is associated with response to atenolol in people with Hypertension.
Notes: 50 mg/day atenolol for twelve weeks.  C carriers MAY respond to this.  Association was not significant.
Article: Influences of UGT2B7 rs7439366 and rs12233719 Polymorphisms on Fentanyl Sensitivity in Chinese Gynecologic Patients
Gene: UGT2B7
Variant/haplotype: rs12233719
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fentanyl in women with Pain, Postoperative as compared to allele G.
Notes: No significant differences in postoperative fentanyl consumption or VAS scores at 24 hours post-surgery between genotypes. Data was not presented in the paper.
Article: STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways
Gene: IL6
Variant/haplotype: rs1800797
Drug(s): opioids
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with decreased dose of opioids in children with Neoplasms and Pain as compared to allele G.
Article: Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis
Gene: XRCC1
Variant/haplotype: rs1799782
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to genotype GG.