shlokn/autogkb huggingface dataset:
Article: Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
Variant/haplotype: rs6083538
Drug(s): "diuretics", "hydrochlorothiazide", "Thiazides, plain"
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with increased response to diuretics, hydrochlorothiazide or Thiazides, plain in people with Hypertension as compared to allele C.
Notes: There was a trend in results but significance was not attained. Association with systolic BP reduction was closest to being significant.  Observations: 2.91 mm Hg increased reduction of systolic blood pressure per T allele in PEAR + GERA, 0.41mm Hg increased reduction of systolic blood pressure per T allele in NORDIL, and 2.34 mm Hg increased reduction of systolic blood pressure per T allele in PEAR + GERA + NORDIL.
Article: Factors Associated with Variability in Rifampin Plasma Pharmacokinetics and the Relationship between Rifampin Concentrations and Induction of Efavirenz Clearance
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): rifampin
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype GG is associated with decreased clearance of rifampin in healthy individuals as compared to genotypes AA + AG.
Notes: Higher Cmax concentrations of rifampin were observed in individuals with the GG genotype.
Article: Atazanavir pharmacokinetics in genetically determined CYP3A5 expressors versus non-expressors
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): atazanavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased clearance of atazanavir in healthy individuals as compared to genotypes AG + GG.
Notes: For the haplotype "1236C/2677G/3435C" "subjects with zero CGC copies had faster atazanavir CL/F and lower Cmin compared with individuals with one or two CGC copies"(complemented to plus chromosomal strand). In this two-phase study, healthy participants were given atazanavir only for 7 days and then were co-administered ritonavir as a booster for days 8-14. The results here are for day 1-7 (atazanavir alone). By the end of day 7 oral clearance of atazanavir was 0.25, 0.18, 0.17 L/h/kg in people with 0, 1 or 2 copies of the haplotype, respectively. Cmin was 66, 159 and 209 ng/mL in people with 0,1 or 2 copies, respectively.
Article: Pharmacogenetics and Pharmacokinetics of Moxifloxacin in MDR-TB Patients in Indonesia: Analysis for ABCB1 and SLCO1B1
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): moxifloxacin
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AC is not associated with increased exposure to moxifloxacin in people with Drug Resistance and Tuberculosis as compared to genotype CC.
Notes: Alleles complemented. "This study found no association between genotype variations in ABCB1 and SLCO1B1 and the AUC0–24 and Cmax of moxifloxacin." The majority of patients were CC (n=38) or AC (n=34) with AA (n=4), AT (n=2) and CT (n=2). There was wide variety of AUCs.
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs581111
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele A.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.; Please note that alleles have been complemented to the positive strand.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: KIF6
Variant/haplotype: rs20455
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with clearance of tenofovir in people with HIV Infections as compared to allele A.
Notes: Significance threshold was set at 3.3E-3.
Article: Pharmacokinetics of Tamoxifen and Its Major Metabolites and the Effect of the African Ancestry Specific CYP2D6*17 Variant on the Formation of the Active Metabolite, Endoxifen
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*17
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *17 is associated with increased exposure to endoxifen in healthy individuals as compared to CYP2D6 *1 + *2.
Notes: Authors looked at CYP2D6*1/*1, *1/*2 or *2/*2 v CYP2D6*1/*17 or *2/*17 v CYP2D6*17/*17. Volunteers were mostly men (n=39, women n=3), received 20mg tamoxifen.
Article: Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in post-menopausal patients with breast cancer
Gene: AKR7A2
Variant/haplotype: rs1043657
Drug(s): exemestane
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with concentrations of exemestane in women with Breast Neoplasms as compared to genotype CC.
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: Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9 intermediate metabolizer
Drug(s): valproic acid
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 intermediate metabolizer is associated with increased concentrations of valproic acid as compared to CYP2C9 normal metabolizer.
Notes: "Compared with the respective normal metabolizers, we observed increased valproate plasma concentrations in CYP2C9 intermediate metabolizers (12% [95% CI, 4%-20%]), CYP2C19 intermediate metabolizers (12% [95% CI, 2%-24%]) and CYP2C19 poor metabolizers (20% [95% CI, 2%-41%]) (Table 3)." Decreased activity: CYP2C9*2: rs1799853; Abolished activity: CYP2C9*3: rs1057910
Article: Human Polymorphisms in the Glutathione Transferase Zeta 1/Maleylacetoacetate Isomerase Gene Influence the Toxicokinetics of Dichloroacetate
Gene: GSTZ1, POMT2
Variant/haplotype: rs1046428
Drug(s): dichloroacetic acid
Phenotype category: Toxicity, Metabolism/PK
Significant: no
Association: Allele T is associated with decreased clearance of dichloroacetic acid in children Mitochondrial Diseases.
Notes: The statement above is meant for a haplotype rather than for the allele. For the various possible haplotype combinations involving rs7975,rs7972,rs1046428, the slowest clearance and the highest urinary excretion of unmetabolized C(13)-DCA was observed for a subject homozygous for G for rs7975,G for rs7972, T for rs1046428.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: AIDA
Variant/haplotype: rs3008634
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of vancomycin as compared to allele C.
Notes: The SNP was not associated with trough levels of vancomycin (first vancomycin trough documented in EMR after at least 3 doses vancomycin). Elimination constants were also calculated.
Article: β-Adrenergic Receptor Polymorphisms and Response to Salmeterol
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): salmeterol
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to salmeterol in people with Asthma as compared to genotype GG.
Article: Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients
Gene: ABCB1
Variant/haplotype: rs17160359
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is associated with increased response to capecitabine and fluorouracil in people with Neoplasm Metastasis as compared to allele G.
Notes: pfSNP identified 2800 SNPS associated with key-words: 5-FU, capecitabine and oxilaplatin and colorectal cancer. Various criteria were used to determine 1536 SNPs to genotype. These SNPs were genotyped in a discovery cohort (N=62) and tested in a validation cohort (N=27). Both cohorts consisted of patients with colorectal cancer metastasis in liver. Five SNPs (rs2289310 G>T; rs1047840 G>A;  rs17431184 T>C; rs17160359 G>T; rs2236722 A>G)  were identified as distinguishing the "non-responder" phenotype from the "responder" phenotype when using a logistic regression multivariate model. The AUC for the receiver operating characteristic curve of the 5 SNPs is 0.875. This logistic-based multivariate model is said to be able to identify 39.1% of non-responders.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs761666827
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele T is not associated with metabolism of nicotine as compared to allele G.
Notes: Assigned as neutral function following in vitro assessments, in vivo associations and variant construct functional assignments.
Article: Translesion Polymerase Genes Polymorphisms and Haplotypes Influence Survival of Osteosarcoma Patients
Gene: REV1
Variant/haplotype: rs3087403
Drug(s): cisplatin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT are associated with increased response to cisplatin in people with Osteosarcoma as compared to genotype CC.
Notes: Presence of at least one T allele is associated with reduced event-free survival (p = 0.004) and overall survival (p < 0.001), with followup until recurrence or death, with a mean follow-up of 143 months.
Article: Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): phenytoin
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C9 *1/*2 is not associated with concentrations of phenytoin in children with as compared to CYP2C9 *1/*1.
Article: CYP2B6 18492T→C Polymorphism Compromises Efavirenz Concentration in Coinfected HIV and Tuberculosis Patients Carrying CYP2B6 Haplotype *1/*1
Gene: CYP2B6
Variant/haplotype: rs2279345
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CC + CT are associated with increased metabolism of efavirenz in people with HIV Infections as compared to genotype TT.
Notes: Significantly lower efavirenz plasma levels were observed in patients with the CC genotype compared to TT at 12 weeks of antiretroval treatment (during anti-TB treatment which included rifampin), and at 24 weeks (after rifampin discontinuation). Significantly lower efavirenz plasma levels were observed in patients with the CT genotype compared to TT only at 24 weeks (after rifampin discontinuation). All patients had the CYP2B6*1/*1 haplotype (as determined by 7 SNPs) before being assessed by this SNP. Please note; this SNP was described as 18492T>C (and previous studies by this group provided the rsID). Multivariate analysis of efavirenz plasma levels at weeks 12 and 24 of treatment showed that this SNP significantly contributed with the C allele was associated with decreased efavirenz plasma concentrations (P at 12 week=0.004 and p at 24 week = 0.007).
Article: Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methadone in people with Heroin Dependence as compared to allele G.
Notes: This SNP was not significantly associated with compliance with methadone maintenance therapy or 'negative rate of morphine urine test'.; Please note that alleles have been complemented to the positive strand.
Article: Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
Gene: ABCC2
Variant/haplotype: rs3740066
Drug(s): mycophenolic acid
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with decreased concentrations of mycophenolic acid in people with lung transplantation as compared to genotypes CC + TT.
Notes: Concentrations measured as trough blood drug concentrations. Differences in concentrations were seen 3 months after transplant.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: AIDA
Variant/haplotype: rs17011686
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with trough concentration of vancomycin as compared to allele A.
Notes: The SNP was not associated with trough levels of vancomycin (first vancomycin trough documented in EMR after at least 3 doses vancomycin). Elimination constants were also calculated.
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: rs35303484
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with concentrations of efavirenz in people with HIV Infections as compared to genotypes AG + GG.
Article: The magnitude of ivacaftor effects on fluid secretion via R117H-CFTR channels: Human in vivo measurements
Gene: CFTR
Variant/haplotype: rs78655421
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with response to ivacaftor in people with Cystic Fibrosis.
Notes: R117H allele. Assessment of C-sweat in three cystic fibrosis patients. A R117H-7T/F508del patient and a R117H-7T/R117H-7T patient both showed increased C-sweat production when treated with ivacaftor. However, a R117H-5T/F508del patient did not have a C-sweat response to ivacaftor.
Article: Gene‐Wide Tagging Study of the Association Between KCNT1 Polymorphisms and the Susceptibility and Efficacy of Genetic Generalized Epilepsy in Chinese Population
Gene: KCNT1
Variant/haplotype: rs546120
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to antiepileptics in people with Epilepsy, Generalized as compared to allele G.
Notes: No significant differences in genotype frequencies were seen between patients who were responsive to antiepileptic drugs (n=279; those who had not experienced any type of seizure for a minimum of 1 year after receiving antiepileptic drugs) and patients who were resistant to antiepileptic drugs (n=204; those who had at least four seizures during the previous year while trying at least three antiepileptic medications at the maximal tolerated doses). Please note alleles have been complemented to the plus chromosomal strand.
Article: Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort
Gene: SP1
Variant/haplotype: rs784888
Drug(s): metformin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with exposure to metformin as compared to allele G.
Article: Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine
Gene: CYP1A2
Variant/haplotype: rs762551
Drug(s): caffeine
Phenotype category: Other, Metabolism/PK
Significant: yes
Association: Genotype AA is associated with increased metabolism of caffeine as compared to genotype AC.
Notes: this was significant in smokers but not non-smokers.
Article: Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities
Gene: CYP2B6
Variant/haplotype: rs3211371
Drug(s): S-EDDP
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with concentrations of (S)-EDDP as compared to allele C.
Article: Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to methylphenidate in children with Autism Spectrum Disorder as compared to genotypes CG + GG.
Notes: Positive response defined as Clinical Global Impression-Improvement (CGI-I) rating of 'much improved' or 'very much improved', and decrease in Aberrant Behavior Checklist-Hyperactivity subscale of >25% from baseline. This result was not significant when considering correction for multiple testing (p<0.002).
Article: Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases
Gene: ADRA2A
Variant/haplotype: rs1800544
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele C.
Notes: Patients underwent the same naturalistic assessment procedure to evaluate the treatment response, which included the reapplication of the CPRS, CTRS, CGI-S, GAS, CPT and TMT A and B. Treatment responders were defined as follows: patients registering 2 points or greater improvement on the CGI-S and a total GAS score of 60 points or greater (out of 108 subjects 66.6% responded to the treatment, while 33.3% did not). No association for distribution of genotypes according to treatment response. However, multiple logistic regression analysis to examine the relationship between various clinical parameters and treatment response showed that ADRA2A GG genotype (OR=5.6), the presence of a psychiatric comorbidity (OR=5.6) and low SES (OR=2.3) were associated with reduced response to methylphenidate treatment.
Article: Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women
Gene: CHRNA5
Variant/haplotype: rs16969968
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bupropion, nicotine or varenicline in men with Tobacco Use Disorder as compared to genotype GG.
Notes: No significant effect of genotype on likelihood of male subjects being abstinent from smoking at 6 months after starting pharmacotherapy for smoking cessation.
Article: CYP2A6 and the plasma level of 5‐chloro‐2, 4‐dihydroxypyridine are determinants of the pharmacokinetic variability of tegafur and 5‐fluorouracil, respectively, in Japanese patients with cancer given S‐1
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*4, CYP2A6*7, CYP2A6*9
Drug(s): tegafur
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2A6 *4/*9 + *7/*9 + *9/*9 are not associated with decreased clearance of tegafur in people with Neoplasms as compared to CYP2A6 *1/*1.
Notes: Oral clearance. Please note; the alleles  were described in the study as *9 and *4, and here is represented as *9 and *4. Also, the 3' UTR conversion of the *7 allele was not mentioned in the study.
Article: CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction
Gene: CYP2B6
Variant/haplotype: rs2279343
Drug(s): methadone
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG are associated with increased dose of methadone in people with Heroin Dependence as compared to genotype GG.
Notes: Patients with the AA or AG genotype required an increased mean daily methadone dose (mg/day) as compared to those with the GG genotype. Please note that this SNP was found to be in strong LD (D' = 1 and r2 = 0.9) with rs3745274 in this sample population.
Article: Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population
Gene: RELN
Variant/haplotype: rs12705169
Drug(s): aripiprazole, olanzapine, perphenazine, quetiapine, risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to aripiprazole, olanzapine, perphenazine, quetiapine or risperidone in people with Schizophrenia as compared to allele T.
Notes: Response was assessed by changes in PANSS score. A reduction of 50% or more in PANSS score was classified as a good response.
Article: Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients—a genome-wide association study adjusting for smoking habits
Gene: NFIB
Variant/haplotype: rs28379954
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with decreased concentrations of clozapine in people with Schizophrenia as compared to genotype TT.
Notes: GWAS analysis was conducted after adjusting for smoking habits of study participants.
Article: Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Significant: no
Association: Allele C is not associated with decreased dose of warfarin as compared to allele T.
Notes: A significant association between genotype and dose was not found in this study; however, the trend for this association "was consistent with the literature".
Article: Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia
Gene: ABCC4
Variant/haplotype: rs9516519
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.
Notes: All patients received four cycles of high dose MTX (5000mg per square meter of body surface area). 1/10th of the dose was administered over 30 minutes (rapid infusion) and the rest was administered continuously over 24hrs. Leucovorin rescue was administered every 6hrs starting 48 hrs after initiation of MTX infusion.
Article: Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor / lumacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype del/del is associated with increased response to ivacaftor / lumacaftor in people with Cystic Fibrosis as compared to genotypes CTT/CTT + CTT/del.
Notes: This was a pooled analysis, stratifying patients by specific categories of lung function, including severe lung dysfunction with ppFEV less than 40. Some patients experienced respiratory adverse events upon initiation of therapy but these usually resolved with continued therapy. Patients were randomized to receive either 600 mg lumacaftor with 250 mg ivacaftor every 12 hours, or 400 mg lumacaftor with 250 mg ivacaftor every 12 hours, or placebo.
Article: Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study
Gene: FRAS1
Variant/haplotype: rs4386623
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG is associated with increased dose of warfarin in people with heart valve replacement as compared to genotype GG.
Notes: in univariate analysis of patients on stable dose. "FRAS1 rs4386623 A allele carriers necessitated significantly higher warfarin doses compared to non-carriers"
Article: A novel mutant variant of the CYP2D6 gene (CYP2D6 17) common in a black African population: association with diminished debrisoquine hydroxylase activity
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*17
Drug(s): debrisoquine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *1/*17 is associated with decreased metabolism of debrisoquine in healthy individuals as compared to CYP2D6 *1/*1 + *1/*2.
Notes: MR of was higher for *1/*17 (n=23) mean value 1.45. Mean MR values *1/*1(n=12) =0.56 and *1/*2 (n=13)=0.59.