shlokn/autogkb huggingface dataset:
Article: Effects of cytochrome P450 2B6 and constitutive androstane receptor genetic variation on Efavirenz plasma concentrations among HIV patients in Kenya
Gene: CYP2B6
Variant/haplotype: rs2279343
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is associated with increased concentrations of efavirenz in people with HIV Infections as compared to allele A.
Notes: this was significant in preliminary analysis but not in the multivariate analysis. Described as 785A>G
Article: Influence of genetic co-factors on the population pharmacokinetic model for clopidogrel and its active thiol metabolite
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): clopidogrel
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with exposure to clopidogrel as compared to allele G.
Notes: Full pharmacokinetic profile was obtained from 17 subjects at  0.5, 1, 2, 3, and 4 h post clopidogrel dose. From 46 subjects samples were collected at 0.5 and 2 h or 1 and 3 h post-dose. Subjects were receiving PCI or elective coronarography.
Article: Therapeutic Drug Monitoring and Pharmacogenetic Study of HIV-Infected Ethnic Chinese Receiving Efavirenz-Containing Antiretroviral Therapy with or without Rifampicin-Based Anti-Tuberculous Therapy
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GT is associated with decreased clearance of efavirenz in people with HIV Infections as compared to genotype GG.
Notes: Patients with the GT genotype had higher plasma efavirenz concentrations compared to patients with the GG genotype: 2.50 mg/L [0.98-10.00] for GG genotype vs 3.47 mg/L [1.35-8.73] for GT genotype.
Article: RRM1 single nucleotide polymorphism -37C→A correlates with progression-free survival in NSCLC patients after gemcitabine-based chemotherapy
Gene: RRM1
Variant/haplotype: rs9937
Drug(s): carboplatin, gemcitabine
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to carboplatin and gemcitabine in people with Carcinoma, Non-Small-Cell Lung as compared to genotype GG.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Variant/haplotype: rs10458360
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele G.
Article: ABCB1 Polymorphism Is Associated with Higher Carbamazepine Clearance in Children
Gene: CYP1A2
Variant/haplotype: rs762551
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype AA is associated with increased clearance of carbamazepine in children with Epilepsy.
Notes: "In addition to the ABCB1 genotype, the present study confirmed that the male sex, the CYP1A2 −163A/A genotype and higher CBZ daily dosage are associated with increased CBZ clearance". The article does not contain much information about CYP1A2 since it focuses on the association with ABCB1. Annotation done on rs762551 (-163C>A). PharmVar released an updated CYP1A2 nomenclature 12/2024. At this point, -163 C>A was included in 26 core alleles with *30 being the SNP by itself. The 25 other core alleles include the -163 C>A SNP in addition to amino acid changes.
Article: A polymorphism in the VKORC1-regulator calumenin predicts higher warfarin doses in African-Americans
Gene: CALU
Variant/haplotype: rs339097
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele G is associated with increased dose of warfarin.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: CMTM8
Variant/haplotype: rs4627790
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients
Gene: ADRA1B
Variant/haplotype: rs10515807
Drug(s): doxazosin, phenoxybenzamine
Phenotype category: Dosage
Significant: no
Association: Allele G is associated with decreased dose of doxazosin or phenoxybenzamine in people with Pheochromocytoma or Paraganglioma as compared to allele A.
Notes: "The G alleles of rs10515807 in the ADRA1B gene and rs553668 in the ADRA2A gene both caused a three times lower risk of being in a higher dosage step than allele A" "However, none of these significances survived the multiple testing correction."
Article: Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*9, CYP2D6*10, CYP2D6*41
Drug(s): primaquine
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 *4/*41 + *1/*4 + *10/*10 + *10/*41 + *2/*4 + *41/*41 is associated with decreased response to primaquine in people with Malaria as compared to CYP2D6 *1/*10 + *1/*41 + *1/*9 + *2/*10 + *2/*41 + *1/*1 + *1/*2 + *2/*2.
Notes: Please not patients are co-treated with chloroquine. relapse frequency was higher in PQ-treated subjects who were IM (50 %) than in EM subjects (17 %), p = 0.05, odds ratio = 9.18 (95 % CI 1.00, 8). Genotyped with Affymetrix® DMET-Plus array. Phenotype grouping: poor metabolizers two no function alleles; intermediate metabolizers (IM) one null and one decreased function allele or two decreased function alleles, or one null allele and one normal allele; extensive metabolizers (EM) if they carried two normal alleles or one normal allele and one deficient allele.
Article: Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with concentrations of efavirenz in children with HIV Infections as compared to allele T.
Notes: This is stated in the paper, but supporting data is not shown.; Allele also known as CYP3A5*3.
Article: Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia
Gene: CYP3A4
Variant/haplotype: CYP3A4 low activity
Drug(s): n-desmethylclozapine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A4 low activity is associated with decreased concentrations of n-desmethylclozapine in people with Schizophrenia as compared to CYP3A4 high activity.
Notes: Authors state that "strong association was observed between norclozapine formation and CYP3A4 expression", where low expression of CYP3A4 in patients’ peripheral leukocytes was associated with higher clozapine concentrations and lower n-desmethylclozapine (also known as norclozapine), compared to normal/high expression of CYP3A4 in patients’ peripheral leukocytes. Authors did genotype for some CYP1A2 and CYP3A4/5 alleles but these "alleles did not explain the inter-individual differences in CYP3A4 mRNA levels" and "hepatic CYP1A2 and CYP3A4 activities were therefore estimated from mRNA levels in patients’ leukocytes, categorizing the patients into low, normal and high expresser groups"
Article: Sorafenib is an Inhibitor of UGT1A1 but is Metabolized by UGT1A9: Implications of Genetic Variants on Pharmacokinetics and Hyperbilirubinemia
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): sorafenib
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A1 *1/*28 + *28/*28 are associated with increased exposure to sorafenib in people with Neoplasms as compared to UGT1A1 *1/*1.
Notes: patients  carrying  only UGT1A1*28, and possibly UGT1A9*3, alleles are at an; increased risk of elevated sorafenib concentrations, as well as a greater incidence of HFSR. However, there remained a group of patients carrying UGT1A1*28/*28 and ABCC2 -24C>T that had abnormally low sorafenib AUC, thereby complicating this analysis.
Article: The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): allopurinol
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of allopurinol in people with Gout as compared to allele G.
Notes: ABCG2 genotype and diuretic use explained 53% of the variability in prediction error.
Article: Early Tacrolimus Concentrations After Lung Transplant are Predicted by Combined Clinical and Genetic Factors and Associated with Acute Kidney Injury
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3, CYP3A5*6, CYP3A5*7
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *3/*3 + *6/*6 + *7/*7 + *3/*6 + *3/*7 + *6/*7 (assigned as poor metabolizer phenotype) are associated with decreased metabolism of tacrolimus in people with lung transplantation as compared to CYP3A5 *1/*1 + *1/*3 + *1/*6 + *1/*7 (assigned as intermediate metabolizer and normal metabolizer phenotype) .
Notes: Patients who were poor metabolizers had roughly 50% higher tacrolimus concentration:dose ratio (CDR) values compared with; intermediate and extensive metabolizers, consistent with reduced tacrolimus metabolism. Absolute tacrolimus concentrations were higher in these patients as well. "A model with clinical and pharmacogenetic factors explained 42% of concentration variance compared with 19% for pharmacogenetic factors only." "Early tacrolimus exposure variability is explained in part by CYP3A5 genotype, but clinical factors accounted for substantial residual variability."
Article: Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): phenytoin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 *1/*3 + *2/*2 + *2/*3 + *3/*3 are associated with increased concentrations of phenytoin as compared to CYP2C9 *1/*1.
Notes: Compared to CYP2C9 extensive metabolizers, low-intermediate/poor metabolizers had a 21.3-pg/mL increase (95% CI: 13.6–29.0pg/mL; P<0.01)
Article: Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report
Gene: DRD2
Variant/haplotype: rs1799732
Drug(s): aripiprazole
Phenotype category: Efficacy
Significant: not stated
Association: Genotype G/del is associated with decreased response to aripiprazole in people with schizoaffective disorder.
Notes: A 51 y.o African-American man with schizoaffective disorder, depressive and post-traumatic stress disorder was referred to a community mental health center to address medication non-adherence and lack of medication effectiveness. The patient began treatment with long-acting injectable (LAI) aripiprazole (400 mg) every 4-weeks plus 30 mg/day of oral aripiprazole, which was reduced to 15 mg/day 2-weeks post-injection. 8 weeks later psychiatric symptoms improved and over 12-weeks, dose was reduced to 5 mg/day. Within 4-weeks of this dosing strategy, auditory hallucinations returned and worsened. Oral aripiprazole dose increased to 7.5 mg/day with improvement in symptoms but at 2-week and 3 week follow-ups auditory hallucinations returned so aripiprazole LAI frequency increased to every 3-weeks (and 7.5 mg/day oral). Pharmacogenetic testing revealed the patient to carry the rs1799732 (-141C/ Del) variant (without complement to the + chromosomal strand) and he was switched to 882 mg/3 weeks of injectable aripiprazole lauroxil without oral aripiprazole in December of 2015 and as of February 2017 continues to tolerate the aripiprazole lauroxil and reports not needing oral aripiprazole.
Article: Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with increased exposure to tacrolimus in people with Kidney Transplantation as compared to genotype TT.
Notes: "Concerning the CYP3A4*1.001 allele, the C0/D ratio exhibited a statistically significant difference between carriers and non-carriers across different periods (overall p = 0.016, during 1–14 days p = 0.015, during 31–60 days p = 0.011, and beyond 60 days p = 0.015)." No CC were observed.
Article: Germline Polymorphisms as Biomarkers of Tumor Response in Colorectal Cancer Patients Treated with Anti-EGFR Monoclonal Antibodies: A Systematic Review and Meta-Analysis
Gene: KRAS
Variant/haplotype: rs61764370
Drug(s): cetuximab, panitumumab
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to cetuximab or panitumumab in people with Colorectal Neoplasms as compared to allele A.
Notes: Meta-analysis with 5 studies. The authors did not provide the exact number of patients but stated that "the median number of patients per analysis was 110 (range 50 - 740)". Most definitions of response were variations of the RECIST criteria. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): voriconazole
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 (assigned as intermediate metabolizer phenotype) is associated with increased dose-adjusted trough concentrations of voriconazole in children with Neoplasms as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: *1/*2 is determined as *1/*2A and *1/*2B. Significantly higher trough concentrations (adjusted for daily dose) were observed in patients with the *1/*2A or *1/*2B  diplotypes. None of these patients had therapeutic concentrations. CYP2C19*17 was defined as rs12248560 c.-806C>T, *2A as rs4244285 c.681G>A, *2B as rs4244285 and rs17878459 c.276G>C, and *1 as none of these variants.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: COMT
Variant/haplotype: rs4680
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with decreased response to risperidone in people with Schizophrenia as compared to allele G.
Notes: The A allele was initially significantly more frequent in patients designated as non-responders to risperidone (i.e. <50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.
Article: Gene Variants in CYP2C19 Are Associated with Altered In Vivo Bupropion Pharmacokinetics but Not Bupropion-Assisted Smoking Cessation Outcomes
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): bupropion
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C19 *17 is not associated with exposure to bupropion in healthy individuals as compared to CYP2C19 *1.
Notes: Healthy volunteers were given 150 mg of bupropion once a day for 7 days. On day 7 plasma samples were taken every 4 hours for a 24-hour period as well as a complete urine sample. The steady-state plasma area under the plasma concentration-time curve for bupropion, erythrohydrobupropion and theohydrobupropion or hydroxybupropion did not significantly differ between the CYP2C19*17 allele as compared to the CYP2C19*1.
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: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b or ribavirin in people with Hepatitis C, Chronic as compared to genotypes CT + TT.
Notes: PEG-interferon alfa (2a and b) was co-administered with ribavirin. Response was assessed by sustained virological response (SVR) percent by genotype. HCV RNA <400,000 IU/ml, age, and low stage liver fibrosis were also independently associated with SVR.
Article: Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
Gene: XRCC1
Variant/haplotype: rs1799782
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to Platinum compounds in people with Lung Neoplasms as compared to allele A.
Notes: Pooled odds ratios (ORs) were performed for an allele model, a homozygous model, a heterozygous model, a recessive model and a dominant model. The association was only significant for response rate with the recessive model, but was not associated with overall survival or progression free survival.
Article: Evaluation of CYP2D6 enzyme activity using a Dextromethorphan Breath Test in Women Receiving Adjuvant Tamoxifen
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*9, CYP2D6*10, CYP2D6*41
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *1/*1 + *2/*2 + *1/*2 (assigned as normal metabolizer phenotype) is associated with increased concentrations of endoxifen in women with Breast Neoplasms as compared to CYP2D6 *3/*41 + *4/*9 + *4/*10 + *4/*41 + *3/*4 + *4/*4.
Notes: The patients were treated with tamoxifen. Neither tamoxifen, desmethyltamoxifen, or hydroxytamoxifen pharmacokinetics were found to differ by CYP2D6 genotype.The study found that the CYP2D6 genotype was positively correlated with endoxifen steady-state concentrations at 3 month (r=0.47, P<0.0001, n=57), at 6 month (r=0.56, P<0.0001, n=54) and the ratio endoxifen/desmethyltamoxifen at 3 month (r=0.60, P<0.0001, n=57) and the 6 month (r=0.61, P<0.0001). The article describes a CYP2D6 genotype association without reporting how the metabolizer categories were group together. The study had patients with ultrarapid, extensive, intermediate and poor metabolizer phenotype.
Article: Genetic coding variants in the niacin receptor, hydroxyl-carboxylic acid receptor 2 (HCAR2), and response to niacin therapy
Gene: HCAR2
Variant/haplotype: rs2454727
Drug(s): niacin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with decreased response to niacin as compared to genotype CC.
Notes: The study compared statin + placebo treated patients with statin + extended release niacin treated patients from the from the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH) trial. In White patients, the reduction in lipoprotein (a) [Lp(a)] in response to niacin was greater in subjects with the CC genotype.
Article: Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): fluorouracil, leucovorin, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fluorouracil, leucovorin and oxaliplatin in people with Esophageal Neoplasms and Stomach Neoplasms as compared to allele A.
Article: Effects of Opioid Receptor Gene Variation on Targeted Nalmefene Treatment in Heavy Drinkers
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): nalmefene
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to nalmefene in people with Alcoholism as compared to allele A.
Article: Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease
Gene: PIK3CA
Variant/haplotype: rs67562832
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with increased resistance to clopidogrel in people with Coronary Disease as compared to allele A.
Article: Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG is associated with decreased dose of warfarin in people with Cardiovascular Diseases as compared to genotype GG.
Notes: This SNP was presented as VKORC1 1173C>T. Patients carrying the A allele showed significantly lower doses of warfarin as compared to patients with the wildtype genotype, GG.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: MIA3
Variant/haplotype: rs35822937
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: High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients
Gene: ABCG2
Variant/haplotype: rs12505410
Drug(s): imatinib
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to allele T.
Notes: As part of a haplotype with rs2725252: those with the G-C haplotype (rs12505410-rs2725252) had a significantly higher cumulative incidence major molecular response (CI-MMR) as compared to those with any other haplotype (i.e. G-A, T-C, T-A). This study was done in an exploratory cohort (n=105) and a validation cohort (n=239); within the validation cohort, patients were either taking a 400mg/day dose of imatinib (n=132) or a 600mg/day dose (n=107). Results were NOT significant for those taking a 600mg/day dose. Please note that alleles for rs2725252 have been complemented to the plus chromosomal strand.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: ARHGEF28
Variant/haplotype: rs929740
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.