shlokn/autogkb huggingface dataset:
Article: Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): nevirapine
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotypes GT + TT are associated with decreased clearance of nevirapine in people with HIV Infections as compared to genotype GG.
Notes: GT + TT were associated with increased exposure to drug, as measured by increased area under the concentration time curve and decreased apparent oral clearance of the drug. This was not statistically significant after multiple comparison correction, but was significant in a multiple variant model for nevirapine AUC (p=0.0001) [stat_test: linear regression]
Article: Impact of CYP2C19 Genotype and Liver Function on Voriconazole Pharmacokinetics in Renal Transplant Recipients
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C19 *1/*1 is associated with increased metabolism of voriconazole in people with Kidney Transplantation as compared to CYP2C19 *1/*2 + *1/*3 + *2/*17.
Notes: Patients who are CYP2C19 extensive metabolizers (EMs, *1/*1) had decreased trough concentrations of voriconazole (Cmin) as compared to intermediate metabolizers (IMs, *1/*2, *1/*3 or *2/*17). However, note that the authors did not specifically state which of these IM genotypes were present in the population. Receiving voriconazole for prevention or treatment of invasive fungal infection (IFI).
Article: Effects of CYP2C19 genetic polymorphisms on the cure rates of H. pylori in patients treated with the proton pump inhibitors: An updated meta-analysis
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizer and intermediate metabolizer genotypes
Drug(s): lansoprazole, omeprazole
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 intermediate metabolizer and poor metabolizer is associated with increased clinical benefit to lansoprazole or omeprazole in people with Helicobacter Infections as compared to CYP2C19 normal metabolizer.
Notes: in meta-analysis of cure rates of H. pylori in triple therapy.
Article: Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele A is associated with dose of warfarin as compared to allele G.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: CYP2C9
Variant/haplotype: rs9332245
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AT is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype TT.
Notes: from TABLE 4 Ticagrelor pharmacokinetic parameters based on genotypes without statistical significance and TABLE 5; AR-C124910XX pharmacokinetic parameters based on genotypes without statistical significance
Article: Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy
Gene: CYP19A1
Variant/haplotype: rs4646
Drug(s): hdl cholesterol
Phenotype category: Other
Significant: yes
Association: Allele A is associated with decreased concentrations of hdl cholesterol in women with Breast Neoplasms and Menopause as compared to allele C.
Notes: when taking letrozole alone or with lipid lowering agents (LLA), such as statins. Data are from a sub-analysis of the Exemestane and Letrozole Pharmacogenomics (ELPh) study, where post-menopausal women with early stage breast cancer were randomized to receive exemestane or letrozole. Of the 303 eligible women, 160 were randomized to the letrozole group, 52 of whom were also taking LLA. This SNP was associated with decreases in HDL-cholesterol of 4.2 mg/dL (SE 1.16).
Article: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs1610696
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotypes CG + GG are not associated with response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). Neither were significantly associated with any genotype.
Article: Genetic Variation in CYP3A43 Explains Racial Difference in Olanzapine Clearance
Variant/haplotype: rs2572023
Drug(s): olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of olanzapine in people with Schizophrenia as compared to allele G.
Article: Translesion Polymerase Genes Polymorphisms and Haplotypes Influence Survival of Osteosarcoma Patients
Gene: REV1
Variant/haplotype: rs3087386
Drug(s): cisplatin
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AG are not associated with increased response to cisplatin in people with Osteosarcoma as compared to genotype GG.
Notes: This SNP is not associated with event-free survival (p = 0.744) or overall survival (p = 0.189), as determined by recurrence or death. Mean follow-up time was 143 months.
Article: Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients
Gene: CYP2C9
Variant/haplotype: rs7900194
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele A is associated with decreased dose of warfarin as compared to allele G.
Notes: This SNP defines CYP2C9*8. CYP2C9 *2,*3,*4,*5,*8 were grouped into three groups for testing: *1/*1 vs. *1/*2 + *1/*3 + *1/*4 + *1/*5 + *1/*8 vs *2/*2 + *2/*3 + *3/*3 + *5/*5. People having one or two variant alleles had lower dose requirements than people who were *1/*1.
Article: Race, Gender, and Genetic Polymorphism Contribute to Variability in Acetaminophen Pharmacokinetics, Metabolism, and Protein-Adduct Concentrations in Healthy African-American and European-American Volunteers
Gene: UGT1A
Variant/haplotype: rs8330
Drug(s): acetaminophen
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of acetaminophen in healthy individuals as compared to allele G.
Article: Genetic Variation in BDNF is Associated with Antipsychotic Treatment Resistance in Patients with Schizophrenia
Gene: BDNF
Variant/haplotype: rs6265
Drug(s): antipsychotics
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with increased resistance to antipsychotics in people with Schizophrenia as compared to genotype CC.
Notes: The T allele is associated with increased odds of resistance to antipsychotic treatment. Resistance was assessed by whether patients were taking clozapine, since clozapine is indicated for patients poorly responsive or resistant to first-line treatments. Please note alleles have been complemented to the plus chromosomal strand.
Article: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and Phe508del and a Residual Function Mutation
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype CTT/del is associated with increased response to ivacaftor in people with Cystic Fibrosis.
Notes: This trial was designed to evaluate the efficacy and safety of tezacaftor with ivacaftor, ivacaftor monotherapy, or placebo. It is a phase 3, randomized, multicenter, double-blind, placebo-controlled, two-period, three-intervention crossover trial (NCT02392234). Patients were 12 years of age or older with cystic fibrosis (CF) and were heterozygous for the Phe508del CFTR mutation and a second allele with a CFTR mutation with residual function as assessed by in vitro studies. Each patient received two of the three regimens (tezacaftor with ivacaftor, ivacaftor monotherapy, or placebo).
Article: A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania
Gene: G6PD
Variant/haplotype: G6PD deficiency
Drug(s): primaquine
Phenotype category: Efficacy
Significant: no
Association: G6PD deficiency is not associated with decreased clinical benefit to primaquine in children with Malaria as compared to G6PD non-deficient.
Notes: Authors measured "two most common polymorphisms associated with G6PD deficiency in Africa i.e., A376G (rs1050829 A > G/T > C) and G202A (rs1050828 G > A/C > T) " and "The outcomes were classified as follows; For males A was defined as wild-type/normal and A− as hemizygous/deficient G6PD status, whereas for females A−A− was defined as homozygous/deficient, AA− and BA− as heterozygous/intermediate and AA and BA as wild-type/normal G6PD status".  Hemizygous/homozygous G6PD deficient, n = 20, and G6PD heterozygous female, n = 21. "none of the patients had parasitaemia on day 3"
Article: Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Genotype GG is associated with increased dose of warfarin as compared to genotypes AA + AG.
Notes: Univariate analysis only. Association was significant in the overall group, and in the self-reported "non-white" patients, but not in the self-reported "white" patients.
Article: Influence of IL-18 and IL-10 Polymorphisms on Tacrolimus Elimination in Chinese Lung Transplant Patients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased dose-adjusted trough concentrations of tacrolimus in people with lung transplantation as compared to genotypes CT + TT.
Notes: Patients with the CC genotype had higher dose-adjusted trough concentrations of tacrolimus at weeks 1 (p=0.005), 2 (p=0.008), 3 (p=0.003) and 4 (p<0.001) post-transplant as compared to those with the CT or TT genotype. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Genotypes CT + TT is not associated with resistance to clopidogrel in people with Stroke as compared to genotype CC.
Article: Genome-Wide Prioritization and Transcriptomics Reveal Novel Signatures Associated with Thiazide Diuretics Blood Pressure Response
Gene: VASP
Variant/haplotype: rs10995
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: The rs10995 G-allele was associated with better blood pressure response to hydrochlorothiazide versus noncarriers (delta systolic BP/delta diastolic BP: -12.3/-8.2 versus -6.8/-3.5 mm Hg, respectively, delta systolic BP P=3×10-4, delta diastolic BP P=5×10-5)". rs10995 G-allele was associated with increased mRNA expression of VASP (vasodilator-stimulated phosphoprotein).
Article: Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states1
Gene: APOA5
Variant/haplotype: rs3135506
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: not stated
Association: Genotypes CG + GG are associated with increased response to fenofibrate in people with Hypertriglyceridemia.
Notes: When combined with rs780094 CT + TT genotypes. This combined genotype group is associated with a greater reduction in triacylglycerol concentrations between baseline and 3 weeks of treatment, as compared to any other genotype combination. Adjusted for baseline triacylglycerol.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs2226443
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of tenofovir in people with HIV Infections as compared to allele T.
Notes: Significance threshold was set at 5E-9. This variant was in strong linkage disequilibrium with rs4816969 and rs9305223.
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: OPRM1
Variant/haplotype: rs6902403
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methadone in people with Heroin Dependence as compared to allele T.
Notes: This SNP was not significantly associated with compliance with methadone maintenance therapy or 'negative rate of morphine urine test'.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele T.
Notes: Methadone maintenance dose was not associated with genotype of the SNP but it was correlated to the highest dose ever used. Multiple doses versus single dose, body weight, history of cocaine dependence and ethnicity (Asian>Caucasian>African) were independently associated with methadone dose in multiple regression analysis. Please note: alleles have been complemented to the + chromosomal strand.
Article: Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate
Gene: CYP2B6
Variant/haplotype: CYP2B6 poor metabolizer
Drug(s): buprenorphine, methadone
Phenotype category: Efficacy
Significant: no
Association: CYP2B6 poor metabolizer is not associated with response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to CYP2B6 intermediate metabolizer and normal metabolizer.
Notes: Response defined by changes in the rate of dropout from treatment between metabolizer phenotypes. Study genotyped for the CYP2B6 *1, *4, *6 and *9 alleles and then assigned metabolizer phenotypes.
Article: A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose
Gene: CACNA1C
Variant/haplotype: rs216013
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of warfarin.
Notes: This intronic variant in the membrane calcium-channel gene CACNA1C was correlated with warfarin dose (p = 9.2 × 10-5) in the index population (n = 181) from a GWAS study of white patients undergoing anticoagulation therapy. Combined analysis of the index and replication populations (n = 374) yielded a p value of 8.6 × 10-7. "However, this variant did not reach established significance threshold independently in the replication population (P = .002), nor did it achieve significance after multiple testing correction in multivariate modeling (uncorrected P = .003)".
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: APOA4
Variant/haplotype: rs5090
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: no
Association: Genotype CG is 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: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain
Gene: COMT
Variant/haplotype: rs6269
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele A is associated with decreased dose of morphine in people with Neoplasms as compared to allele G.
Notes: This was for alleviation of pain from cancer.  The association was as part of a haplotype consisting of 11 rsIDs (the other rsIDs are rs2075507,rs7287550, rs5746849, rs737866, rs6269, rs740603, rs4818, rs4680, rs174699, rs165728).  The haplotype was associated with a dose reduction factor of 0.71 .  Authors state that because the SNPs are linked, a strict Bonferroni correction is too conservative; however, that is what has been done here for p value.  Also noted was that the carriers of haplotype 1 have had the cancer diagnosis longer than have carriers of other haplotypes, and so the true difference in morphine requirements may be even greater than observed here.
Article: Association between single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) and self-reported responses to alcohol in American Indians
Gene: OPRM1
Variant/haplotype: rs2075572
Drug(s): ethanol
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to ethanol as compared to allele C.
Notes: Please note that alleles have been complemented to the positive strand. The G allele was associated with increased scores in the dizzy, drunk and nausea traits on the Subjective High Assessment Scale-Expectations (SHAS-E) questionnaire.
Article: CYP2D6 Phenotyping Using Urine, Plasma, and Saliva Metabolic Ratios to Assess the Impact of CYP2D6∗10 on Interindividual Variation in a Chinese Population
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*10
Drug(s): dextromethorphan
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *10/*10 is associated with decreased metabolism of dextromethorphan in healthy individuals as compared to CYP2D6 *1/*1.
Notes: Single dose study with 15mg dextromethorphan DM. Urine, Plasma, and Saliva Metabolic Ratios were accessed. Subjects were  genotyped by DNA sequencing analysis for CYP2D6*1, *2, *3, *4, *6, *7, *10, *14, *18, *21, *28, *33, *34, *35, *36, *39, *41, *43, *49, *51, *52, *54, *60, *63, *65, *69, *71, and *75 and CNV were determined. *1/*1 n= 22; *10/*10 n=85. The urinary, plasma, or salivary MRs increased successively in subjects with CYP*1/*1, *1/*10, *10/*10, and *5/*10 with statistical significance (all P-values < 0.001).
Article: Population pharmacokinetics of tacrolimus in children with nephrotic syndrome
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *3/*3 is associated with decreased clearance of tacrolimus in children with Nephrotic Syndrome as compared to CYP3A5 *1/*1.
Notes: One-compartment model and first-order elimination were used for covariate analysis: body weight, CYP3A5 were significantly associated with tacrolimus pk.  Monte  Carlo  simulation  showed that patients w/the CYP3A5*3/*3 genotype receiving 0.10 mg/kg/dose 2x day and patients w/the CYP3A5*1/*1 + *1/*3A receiving 0.25 mg/kg/dose 2x day achieves target concentrations of 5-10 ng/ml. CL/F was significantly lower in CYP3A5*3/*3 vs *1/*1 +*1/*3 (0.567 ± 0.216 vs. 1.050 ± 0.641 L/h/kg, P = 0.005)
Article: Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation: A multicentre prospective cohort study
Gene: PRKAG2
Variant/haplotype: rs12703159
Drug(s): rivaroxaban
Phenotype category: Toxicity
Significant: no
Association: Allele C is associated with increased response to rivaroxaban in people with Atrial Fibrillation as compared to allele T.
Notes: as measured by peak anti‐FXa level. Association described as "suggestive". "The incidence of bleeding events were significantly related to the peak anti‐FXa level, which were significantly increased in patients with bleeding events than in those without"
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: DRD4
Variant/haplotype: rs3758653
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele T.
Notes: Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).
Article: Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP)
Gene: CTLA4
Variant/haplotype: rs231775
Drug(s): avatrombopag, corticosteroids, eltrombopag, rituximab
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with increased clinical benefit to avatrombopag, corticosteroids, eltrombopag or rituximab Thrombocytopenia as compared to allele G.
Notes: "There was no correlation between CTLA-4 (rs: 231775 and rs: 3087243) A/G SNPs were not correlated to the response to all lines of therapy assessed (corticosteroids, thrombopoietin receptor agonists, splenectomy, and rituximab)."
Article: CYP3A4 and CYP3A5 Polymorphisms and Blood Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): amlodipine
Phenotype category: Efficacy
Significant: no
Association: Genotypes CT + TT are not associated with response to amlodipine in men with Hypertension as compared to genotype CC.
Notes: No significant change in the likelihood of a man reaching a target mean arterial pressure concentration of <= 92 mmHg or <= 107 mmHg was seen between genotypes. Please note alleles have been complemented to the plus chromosomal strand.
Article: Subjective Response to Alcohol among Alcohol Dependent Individuals: Effects of the Mu-Opioid Receptor (OPRM1) Gene and Alcoholism Severity
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Toxicity
Significant: yes
Association: Allele G is associated with increased response to ethanol in people with Alcoholism as compared to allele A.
Notes: Participants with the G allele reported greater alcohol-induced stimulation, vigor and positive mood than participants with the AA genotype.
Article: Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of tacrolimus in children with Kidney Transplantation as compared to genotype CT.
Notes: Dose-corrected tacrolimus exposure (AUC0-12/doseBW). Mapped *1B to rs2740574 C and *1A to rs2740574 T based on PharmVAR consolidation of core alleles.
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: POU2F2
Variant/haplotype: rs195854
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to platinum in people with Lung Neoplasms as compared to allele A.
Notes: 26 SNPs were selected which satisfied the following criteria: 1) SNPs were from HapMap Project Phase II of the Han Chinese population 2) were haplotype tagger SNPs 3) SNP minor allele frequency was higher than 5% in Han Chinese 4) the pairwise linkage disequilibrium correlation coefficient (r-squared) was greater than 0.8. After Bonferroni corrections no SNPs remained significantly associated with platinum drug efficacy.
Article: Intestinal CYP3A4 and Midazolam Disposition in vivo Associate with VDR Polymorphisms and Show Seasonal Variation
Gene: VDR
Variant/haplotype: rs11568820
Drug(s): midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with increased clearance of midazolam as compared to genotype CC.