shlokn/autogkb huggingface dataset:
Article: Sodium channel mutation SCN1A T875M, D188V and associated dysfunction with drug resistant epilepsy
Gene: SCN1A
Variant/haplotype: rs121917953
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AT is associated with increased resistance to antiepileptics in people with Epilepsy as compared to genotype TT.
Notes: "The AT genotype exhibited significantly higher risk association with drug resistance with an odds ratio of 3.51 (95%CI = 1.256-3.826 and a P value = 0.017; Table 3)." AA also had increased risk but not significant. grouped p value not shown. Drug regimens not specified
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs7841320
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of tenofovir in people with HIV Infections as compared to allele G.
Notes: Significance threshold was set at 6E-7.
Article: VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *3 is not associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: in Alaska Native and American Indian People.
Article: A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin as compared to allele C.
Article: Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): axitinib
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with concentrations of axitinib in people with Carcinoma, Renal Cell as compared to allele C.
Notes: The authors develop a prediction model and calculated area under the concentration curve (AUC) using 6 SNPs (rs17868323, rs3832043, rs2231142, rs2032582, rs1045642, rs35305980) was compared with actual AUC in 16 patients prospectively which significantly correlated with the objective response rate (P = 0.0002), hand-foot syndrome, P = 0.0055 and hypothyroidism, P = 0.0381, and correlated with actual AUC (P < 0.0001) - the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066).
Article: OPRM1, OPRK1 and COMT Genetic Polymorphisms Associated with Opioid Effects on Experimental Pain: A Randomized, Double-Blind, Placebo-Controlled Study
Gene: OPRK1
Variant/haplotype: rs16918875
Drug(s): butorphanol
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to butorphanol in healthy individuals as compared to allele G.
Notes: Study-wide significance was set to p<0.017.
Article: Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in post-menopausal patients with breast cancer
Gene: CYP1B1
Variant/haplotype: rs10012
Drug(s): exemestane
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CC + CG are not associated with concentrations of exemestane in women with Breast Neoplasms as compared to genotype GG.
Notes: No significant difference in exemestane concentrations were seen between the three genotypes. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy
Gene: SCN4A
Variant/haplotype: rs80338792
Drug(s): flecainide
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is associated with increased response to flecainide in people with Myotonia as compared to allele C.
Notes: This case study showed two patients (mother and son) who both had the same genetic variant (presented in the paper as SCN4A G1306E) causing myotonia permanens. After years of poor response to mexiletine, patients were switched to flecainide and saw huge improvements. This suggests that patients with this myotonia permanens causing variation may benefit more from treatment with flecainide than mexilitine.
Article: Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients
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 increased dose of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: "However, CYP3A5 expressers required tacrolimus dosages 2-fold higher during follow-up and exhibited significantly lower C/D ratios than did nonexpressers. We detected no significant differences between expressers and nonexpressers in the incidence of delayed graft function, rejection, CNI nephrotoxicity, and development of de novo anti-HLA antibodies and de novo DSAs after the follow-up period of 2 years. Renal allograft function was also well preserved in both groups during follow-up." Only *3 was measured.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs9322447
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele A.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: Pharmacogenetic association of the APOA1/C3/A4/A5 gene cluster and lipid responses to fenofibrate: the Genetics of Lipid-Lowering Drugs and Diet Network study
Gene: APOA1
Variant/haplotype: rs11216158
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AG are not associated with response to fenofibrate in people with Hypertriglyceridemia as compared to genotype GG.
Notes: No significant difference in the change in plasma triglyceride (TG) or high-density lipoprotein (HDL) levels between genotypes was seen, after three weeks of treatment with fenofibrate.
Article: Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway
Gene: PON2
Variant/haplotype: rs2299267
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to antidepressants in people with Depressive Disorder, Major as compared to allele A.
Notes: Identity of minor allele not specified, so minor allele of dbSNP used here (G). Response considered to be successful with a 50% reduction at discharge of the Hamilton Rating Scale for Depression (HRSD17). Patients measured at admission and discharge, 4-6 weeks later. Specific antidepressants not listed.
Article: The impact of SLCO1B1 polymorphisms on the plasma concentration of lopinavir and ritonavir in HIV-infected men
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with trough concentration of ritonavir in men with HIV Infections as compared to allele T.
Notes: No significant association between this variant and trough concentrations of ritonavir in HIV patients treated with lopinavir/ritonavir. Variant referred to in the paper as 521T>C.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: DRD2
Variant/haplotype: rs1800497
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele G.
Notes: No significant difference in allele frequency between responders and non-responders. Please note that alleles have been complemented to the positive strand.
Article: Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4‐hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus
Gene: NR1I2
Variant/haplotype: rs13059232
Drug(s): cyclophosphamide
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of cyclophosphamide in people with as compared to allele T.
Notes: This SNP had a small effect on cyclophosphamide (CPA) metabolite plasma concentrations (4-OH-CPA), but did not reach significance (Bonferroni corrected p-value= 0.0056).
Article: Association study between clinical response to rizatriptan and some candidate genes
Gene: DRD2
Variant/haplotype: rs1799732
Drug(s): rizatriptan
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to rizatriptan in people with Migraine without Aura as compared to allele del.
Notes: No significant difference in allele frequency between responders and non-responders to rizatriptan. Variant referred to in the paper as DRD2-BstNI and mapped to rs1799732 by PharmGKB.
Article: CYP2C19 genotype and sodium channel blockers in lacosamide-treated children with epilepsy: two major determinants of trough lacosamide concentration or clinical response
Gene: CYP2C19
Variant/haplotype: CYP2C19 normal metabolizer
Drug(s): lacosamide
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 normal metabolizer is associated with decreased exposure to lacosamide in children with Epilepsy as compared to CYP2C19 intermediate metabolizer and poor metabolizer.
Notes: "Patients with the NM phenotype exhibited lower drug exposure levels when compared to the IM and PM groups (β = −0.189, p < 0.001; Table 2). This pattern held true in the add-on therapy group as well, with NM individuals displaying lower exposure levels than IM and PM groups (β = −0.374, p < 0.001; Table 3)."
Article: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs1710
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotypes CC + CG.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). Neither were significantly associated with any genotype.
Article: Pharmacogenetic Variants Associated with Fluoxetine Pharmacokinetics from a Bioequivalence Study in Healthy Subjects
Gene: CYP2D6
Variant/haplotype: rs1065852
Drug(s): fluoxetine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased half-life time of fluoxetine in healthy individuals as compared to allele G.
Notes: "The CYP2D6*10 haplotype, related to decreased CYP2D6 function (poor drug metabolism), was found in only one volunteer (subject 25), based on CYP2D6 rs1065852 (haplotype A/A) and rs11358490 (haplotype C/C). As shown in Table 2, t1/2 was three times higher (106.9 h) for this subject than the overall mean (31.02 h). AUCs and t1/2 were statistically different between genotypes of CYP2D6 rs1065852 (p < 0.001). Stratification of subjects based on CYP2D6 genotypes confirmed the difference in the PK profiles, based on the three SNVs found in this study (rs1065852, rs1135840, and rs28371703)"
Article: Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9
Gene: CYP2C9
Variant/haplotype: rs1799853
Drug(s): piroxicam
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is not associated with response to piroxicam as compared to allele C.
Notes: Subjects had at least one impacted lower third molar extracted. Measurements were taken of 1) postoperative mouth opening (millimeters) was measured pre- and post-op on days 2 & 7 2) and swelling measurements due to edema were recorded and 3) subjective measures of pain. None were associated with the genotype.
Article: Lack of association between plasma levels of non-nucleoside reverse transcriptase inhibitors & virological outcomes during rifampicin co-administration in HIV-infected TB patients
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of efavirenz in people with HIV Infections and Tuberculosis as compared to genotypes GG + GT.
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Gene: CSMD3
Variant/haplotype: rs2432742
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele G.
Notes: There was a trend in results but significance was not attained. Observations: 2.52 mm Hg increased reduction of diastolic blood pressure per A allele in PEAR + GERA, 0.07 mm Hg decreased reduction of diastolic blood pressure per A allele in NORDIL (small, opposite direction effect), and 1.57 mm Hg increased reduction of diastolic blood pressure per A allele in PEAR + GERA + NORDIL.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DBH
Variant/haplotype: rs5320
Drug(s): heroin
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to heroin as compared to allele G.
Notes: No significant association between this variant and strength of euphoria on first heroin use.
Article: Variation in P450 oxidoreductase (POR) A503V and flavin containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism but does not alter cigarette consumption
Gene: POR
Variant/haplotype: rs1057868
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with increased metabolism of nicotine in CYP2A6 normal, but not reduced, metabolizers as compared to genotype CC.
Notes: Participants received 4 mg oral nicotine.  3HC/COT was measured.
Article: Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis
Gene: CFH
Variant/haplotype: rs1061170
Drug(s): bevacizumab, ranibizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to bevacizumab and ranibizumab in people with Macular Degeneration as compared to genotypes CT + TT.
Notes: Neovascular age-related macular degeneration. Meta-analysis with 13 studies. Anti-VEGF treatment was much less effective in patients with the CC genotype as compared to those with the CT or TT genotype. Significant results were also seen when considering exclusively Caucasians, though no significant results were seen when considering exclusively East Asians. 10 of the 13 studies defined a positive outcome from anti-VEGF therapy as improvement in visual function (visual acuity), while the remaining three define it as an improvement in retinal morphology (resolution of macular edema). A sub-analysis was done on studies only considering response as improvement in visual acuity, with significant results.
Article: Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele C is associated with decreased dose of warfarin as compared to allele A.
Notes: CYP2C9*3 was associated with a; 33% (95% confidence interval 29¿37%) decrement in warfarin dose per allele.
Article: Identification of novel CYP2A6*1B variants; the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *46/*46 is associated with increased clearance of nicotine as compared to CYP2A6 *1/*1.
Notes: Includes alleles *1B1-*1B15. Please note that the *46 allele is described as the *1B1 allele in the paper and has subsequently been reassigned by PharmVar.
Article: Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial
Gene: KRAS
Variant/haplotype: rs61764370
Drug(s): capecitabine, cetuximab, oxaliplatin
Phenotype category: Efficacy
Significant: yes
Association: Genotype AC is associated with increased response to capecitabine, cetuximab and oxaliplatin in people with Rectal Neoplasms as compared to genotype AA.
Notes: C allele carriers (there were no homozygotes) had a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy and a trend for better 5-year progression-free survival (PFS) and overall survival. Both CR and survival outcomes were independent of the use of cetuximab. Patients received neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab
Article: Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics
Gene: CYP2C8
Variant/haplotype: CYP2C8*1, CYP2C8*3
Drug(s): montelukast
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C8 *3 is associated with decreased concentrations of montelukast in healthy individuals as compared to CYP2C8 *1/*1.
Notes: This allele is associated with reduced area under the plasma concentration-time curve (AUC) of montelukast (11.3% reduction per copy of each allele, P=0.00659).
Article: NUDT15 R139C Variants Increase the Risk of Azathioprine-Induced Leukopenia in Chinese Autoimmune Patients
Gene: NUDT15
Variant/haplotype: rs116855232
Drug(s): thioguanine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with concentrations of thioguanine in people with Autoimmune Diseases, Lupus Erythematosus, Systemic or Sjogren's Syndrome as compared to allele C.
Notes: after treatment with azathioprine and 6-TGN was not significantly different between patients with leukopenia or the controls.
Article: Germline single nucleotide polymorphisms in ERBB3 and BARD1 genes result in a worse relapse free survival response for HER2-positive breast cancer patients treated with adjuvant based docetaxel, carboplatin and trastuzumab (TCH)
Gene: RNF8
Variant/haplotype: rs2284922
Drug(s): carboplatin, docetaxel, trastuzumab
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to carboplatin, docetaxel and trastuzumab in women with Breast Neoplasms.
Notes: When compared to women who received different treatment regimens. Response was defined as likelihood of achieving relapse-free survival. Please note that alleles have been complemented to the positive strand.
Article: Effect of APOE and CHRNA7 Genotypes on the Cognitive Response to Cholinesterase Inhibitor Treatment at Different Stages of Alzheimer’s Disease
Gene: APOE
Variant/haplotype: rs429358
Drug(s): donepezil, galantamine, rivastigmine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with decreased response to donepezil, galantamine and rivastigmine in people with Alzheimer Disease as compared to genotype TT.
Notes: In patients with moderate to severe Alzheimer's disease only (baseline Mini-Mental State Examination (MMSE) score < 20); in patients with mild Alzheimer's (MMSE >=20) no significant/borderline significant results were seen (p=0.05). Adjusted for gender, age, and baseline MMSE. After 6 months of treatment with cholinesterase inhibitors, those with the E4 allele were more likely to be a non-responder to treatment, as compared to those without the E4 allele. A responder was defined as a patient who showed improvement or no deterioration in cognition comparing MMSE scores at baseline with MMSE scores after 6 months.
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 C is associated with increased response to Drugs used in nicotine dependence in people with Tobacco Use Disorder.
Notes: in haplotype analysis; individuals with haplotype 3 (rs16969968 allele A - rs680244 allele C) 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 3 that were treated with placebo. The ability to quit cigarette smoking were 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: Association study between clinical response to rizatriptan and some candidate genes
Gene: DRD2
Variant/haplotype: rs6275
Drug(s): rizatriptan
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with decreased response to rizatriptan in people with Migraine without Aura as compared to genotype GG.
Notes: The AA and AG genotypes were significantly more frequent in patients classed as non-responders to rizatriptan. Please note that alleles have been complemented to the positive strand. Variant referred to in the paper as DRD2 NcoI and mapped to rs6275 by PharmGKB.
Article: A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation
Gene: CFTR
Variant/haplotype: rs75527207
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: not stated
Association: Genotypes AA + AG are associated with response to ivacaftor in people with Cystic Fibrosis.
Notes: A clinical trial that selected patients with the G551D CFTR mutation (rs75527207 genotype AA or AG). Patients without this mutation were excluded. One patient included in the placebo group was homozygous for F508del (rs113993960 genotype del/del).
Article: Pharmacogenetics of Antiepileptic Drug Efficacy in Childhood Absence Epilepsy
Gene: CACNA1H
Variant/haplotype: rs2753325
Drug(s): lamotrigine
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased clinical benefit to lamotrigine in children with Epilepsy as compared to allele G.
Notes: as measured by minor allele frequency in not–seizure‐free vs seizure-free children. Authors do not specify which allele is minor allele but state "Two synonymous CACNA1H variants, located essentially next to each other (rs2753326 and rs2753325), were associated with greater seizure freedom in the lamotrigine group. Both have global minor allele frequency reported as 0.29 compared to 0.36 in the lamotrigine cohort." This does not seem to match with frequencies in Table 2. Assumed minor allele as same as dbSNP which was A and major allele as G.
Article: A novel CYP2A6 allele (CYP2A6*35) resulting in an amino acid substitution (Asn438Tyr) is associated with lower CYP2A6 activity in vivo
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*35
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2A6 *35/*35 is associated with decreased metabolism of nicotine as compared to CYP2A6 *1/*1.
Article: Genome-wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences
Gene: ZNF536
Variant/haplotype: rs185430475
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of nicotine as compared to allele C.
Notes: Nicotine metabolism was assessed by measuring participants' nicotine metabolite ratio.