shlokn/autogkb huggingface dataset:
Article: Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): siponimod
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C9 *2/*3 + *3/*3 are associated with increased concentrations of siponimod in healthy individuals as compared to CYP2C9 *1/*1.
Notes: The AUC ∞ and AUC last of siponimod were approximately two and fourfold higher in PMs (CYP2C9*2/*3 and CYP2C9*3/*3), respectively, compared with CYP2C9 EMs (CYP2C9*1/*1). The siponimod plasma T½ was also prolonged in subjects with the CYP2C9*2/*3 and CYP2C9*3/*3 genotypes (50.9 and 126 h, respectively) compared with EMs (CYP2C9*1/*1: 28.1 h), suggesting that the reduced CYP2C9 enzymatic activity does not affect the absorption phase of siponimod but prolongs the elimination phase.
Article: Pharmacogenomics study on cadherin 2 network with regard to HIV infection and methadone treatment outcome
Gene: CDH2
Variant/haplotype: rs8094439
Drug(s): methadone
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to methadone as compared to genotypes AG + GG.
Notes: Association between SNP and response to methadone is not directly shown in the paper. Genotype AA is associated with increased concentrations of CDH2 in plasma and individuals with increased CDH2 levels had an improved response to methadone treatment (p=0.005).
Article: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis
Gene: PDE4B
Variant/haplotype: rs12745871
Drug(s): apremilast
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased clinical benefit to apremilast in people with Psoriasis as compared to allele C.
Notes: "Allele-based association tests detected 64 SNPs displaying nominal p values < 0.05 (Table 2) including 10 SNPs with p values ≤ 0.01. " Table 2 shows frequency of minor allele is responders and non-responders. Responder status maybe defined by PASI score improvement greater than 75% after 24–36 weeks of treatment.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs3850736
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 C.
Notes: Significance threshold was set at 6E-7.
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs74546197
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele G.
Notes: The allele did not reach genome wide significance in the discovery or replication cohorts. GWA analyses were performed for two phenotypes: ‘% change in HRSD-17 score’ (% HRSD defined as the change in HRSD-17 score divided by the baseline score) and ‘response’ (defined as greater than or equal to 50% reduction in HRSD-17 score from baseline to 4-week visit).
Article: Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia
Gene: CYP2C8
Variant/haplotype: rs11572080
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is not associated with decreased clinical benefit to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotype CC.
Notes: Alleles complemented. There were no TT homozygotes. "Assessment of molecular response to imatinib based on the BCR-ABL1 transcript level at 12 months. Responders (n = 26); Non-responders (n = 24). " "No statistically significant difference was found between the frequency of GG and GA genotypes of CYP2C8*3 in the two groups (p = 0.1902). "
Article: Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta‐Analysis
Gene: SLC47A1
Variant/haplotype: rs2252281
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele T.
Notes: This variant is not associated with metformin glycemic response assessed as HbA1c reduction in patients on metformin monotherapy.
Article: The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population
Gene: CYP2D6
Variant/haplotype: CYP2D6*4
Drug(s): amitriptyline
Phenotype category: Dosage
Significant: no
Association: CYP2D6 *4/*4 (assigned as poor metabolizer phenotype) is not associated with dose of amitriptyline as compared to CYP2D6 normal metabolizer.
Notes: The study reports on CYP2D6PM (5) compared to EM (18, only phenotypically characterized) but diplotype was only reported for PM. 5 PMs (genotype as *4/*4) were included in the study.
Article: Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer
Variant/haplotype: rs4779584
Drug(s): fluorouracil, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fluorouracil, irinotecan and oxaliplatin in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to allele C.
Notes: SNPs were investigated for their effects on response rate, time to progression and overall survival. After accounting for multiple testing there was no association with any SNPs and outcomes of patients with metastatic colorectal cancer.
Article: Nuclear receptor gene polymorphisms and warfarin dose requirements in the Quebec Warfarin Cohort
Gene: NR1I3
Variant/haplotype: rs2501873
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of warfarin as compared to allele T.
Notes: Warfarin dose requirement was defined as the reported daily dose at 3 months following treatment initiation.
Article: Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus
Gene: KCNJ11
Variant/haplotype: rs5215
Drug(s): sulfonamides, urea derivatives
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to sulfonamides, urea derivatives in people with Diabetes Mellitus as compared to allele C.
Article: CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4-methylene-dioxymethamphetamine in a controlled study in healthy individuals
Gene: CYP2D6
Variant/haplotype: CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*9, CYP2D6*10, CYP2D6*41
Drug(s): 3,4-methylenedioxymethamphetamine
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 *4/*4 + *3/*5 is associated with increased response to 3,4-methylenedioxymethamphetamine as compared to CYP2D6 *4/*10 + *4/*41 + *5/*10 + *5/*41 + *10/*41 + *10/*10 + *4/*9 (assigned as intermediate metabolizer phenotype) .
Notes: Elevations in systolic blood pressure were greater in PMs compared with IMs (P = 0.02, *4/*10(6) *4/*41(4) *5/*10(2) *5/*41(1) *10/*41(4) *10/*10(1) *4/*9 (1)) and EMs (P = 0.01, *1/*3(2) *1/*6(2) *2/*4(15) *2/*5(1) *9/*10(2); *1/*41(4) *1/*10(2) *1/*9(3) *2/*10(3) *2/*41(5); *1/*1(22) *1/*2(23) *2/*2(16) *1/*4 (11)) at 0.6 h (F2,135 = 3.50, P = 0.03) and also tended to be greater at 1 h (F2,135 = 2.49, P = 0.09).
Article: Genetic Polymorphisms of Cytokines Might Affect Postoperative Sufentanil Dosage for Analgesia in Patients
Gene: IL1A
Variant/haplotype: rs17561
Drug(s): sufentanil
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of sufentanil in people with Pain, Postoperative as compared to allele C.
Article: CYP2B6 and bupropion’s smoking cessation pharmacology: the role of hydroxybupropion
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*4, CYP2B6*5, CYP2B6*6, CYP2B6*18, CYP2B6*22
Drug(s): bupropion
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *1/*6 + *1/*18 is associated with decreased metabolism of bupropion in people with Tobacco Use Disorder as compared to CYP2B6 *1/*1 + *1/*4 + *1/*5 + *1/*22 + *22/*22.
Notes: Light smokers. Individuals with one copy of a reduced function allele (*6, *18) were grouped into the "intermediate metabolizer" group. The genotypes within this group were *1/*6 (n=53), *1/*18 (n=8), *1/*6 + *1/*5 (compound heterozygote; n=1), *1/*6 + *1/*22 (compound heterozygote; n=2). Individuals with *1/*1 (n=48), *1/*4 (n=1), *1/*5 (n=4), *1/*22 (n=4), and *22/*22 (n=1) genotype were considered normal metabolizers. Intermediate metabolizers had decreased hydroxybupropion/bupropion ratios as compared to normal metabolizers. No significant result was seen when considering bupropion levels (p=0.056) or hydroxybupropion levels (p=0.052).
Article: Exploring the contribution of genetic variants to high sunitinib exposure in patients with cancer
Gene: GLP1R
Variant/haplotype: rs6923761
Drug(s): sunitinib
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with decreased concentrations of sunitinib in people with Carcinoma, Renal Cell or Gastrointestinal Stromal Tumors as compared to allele G.
Notes: "Only 1 marker reached genome-wide statistical significance, rs6923761 (chromosome 6; P = 7.86  1019), located in the glucagon-like peptide 1 receptor (GLP1R) gene. This SNV had a MAF of 0.3 and an effect size βM of 3.18 (odds ratio 0.04), suggesting that carriers of this variant allele have a decreased sunitinib concentration. "
Article: Variants in the CYP2B6 3′UTR alter in vitro and in vivo CYP2B6 activity: potential role of microRNAs
Gene: CYP2B6
Variant/haplotype: rs1042389
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased metabolism of efavirenz in healthy individuals as compared to genotype CC.
Notes: The rs70950385 and rs1042389 variants were in complete linkage disequilibrium (r2=1, D’=1).
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: AKT1
Variant/haplotype: rs3803300
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to risperidone in people with Schizophrenia as compared to allele T.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis
Gene: UGT1A1
Variant/haplotype: rs4148323
Drug(s): selumetinib
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of selumetinib in healthy individuals as compared to allele A.
Notes: Not associated with AUC, AUC0-12 when allele was assessed within ethnic groups (Asian, White, Black) and when all ethnic groups were pooled together. Only P-values for AUC presented here.
Article: Variants in the CYP2B6 3′UTR alter in vitro and in vivo CYP2B6 activity: potential role of microRNAs
Gene: CYP2B6
Variant/haplotype: rs7246465
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with increased metabolism of efavirenz in healthy individuals as compared to genotype CC.
Notes: "An increase in CYP2B6 activity was also seen among volunteers carrying the rs7246465 variant allele (C/C vs. C/T [38.0% increase; p<0.01] and T/T [67.9% increase; p<0.0001])".
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: CYP3A5 *3/*3 is not associated with response to methadone in people with Opioid-Related Disorders as compared to CYP3A5 *1/*1 + *1/*3.
Notes: No significant difference in genotype or phenotype frequencies between responders and non-responders, as defined by drug misuse during methadone maintenance therapy. No details about which specific variants/alleles were tested for.
Article: OCT1 genetic variants influence the pharmacokinetics of morphine in children
Gene: SLC22A1
Variant/haplotype: rs12208357
Drug(s): morphine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased clearance of morphine in children with adenotonsillectomy as compared to genotypes CC + CT.
Notes: Children with two loss of function SLC22A1 alleles (*2 rs72552763 GAT>del, *3 rs12208357C>T, *4 rs34130495 G>A, or *5 rs34059508 G>A) were grouped together and had significantly lower clearance compared to children with the *1/*1 or *1/variant genotype.
Article: ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection
Gene: ITPA
Variant/haplotype: rs7270101
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotypes AC + CC.
Notes: The authors actually compared platelet counts between patients with normal or deficient ITPase activity. Patients with the composite genotypes of rs1127354 CC and rs7270101 AA had "normal ITPase activity" and all other genotype combinations were classified as "deficient". Univariable logistic regression normal ITPase activity was not significantly associated with virological relapse.
Article: Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2
Gene: CHRNA5
Variant/haplotype: rs588765
Drug(s): cotinine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with concentrations of cotinine in people with Tobacco Use Disorder as compared to allele T.
Notes: The authors conducted a GWAS meta-analysis to identify genetic variants associated with cotinine in current daily smokers (Caucasian). The following study cohorts were analyzed: ALSPAC, CARDIA, FinnTwin, Framingham, GenMets, MESA, NESDA, NTR, TwinsUK, YFS.
Article: Influence of genetic variants on renal uric acid handling in response to frusemide: an acute intervention study
Gene: SLC2A9
Variant/haplotype: rs11942223
Drug(s): furosemide
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to furosemide in healthy individuals as compared to allele T.
Notes: There was no difference in either the absolute values of serum urate, nor in fractiona excretion of uric acid over the study period between those carrying the C allele versus those that did not.
Article: The Missing Association: Sequencing-Based Discovery of Novel SNPs in VKORC1 and CYP2C9 That Affect Warfarin Dose in African Americans
Gene: VKORC1
Variant/haplotype: rs61162043
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: TRIB3
Variant/haplotype: rs2295490
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.
Article: ABCB1 Polymorphism Is Associated with Higher Carbamazepine Clearance in Children
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele A is associated with increased clearance of carbamazepine in children with Epilepsy as compared to allele G.
Notes: Alleles complemented. "Our main finding was that the presence of the ABCB1 1236T-2677T-3435T haplotype was associated with an increased clearance of CBZ in children. " "rs1128503 (1236C>T)"
Article: Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder
Gene: PER3
Variant/haplotype: rs228666
Drug(s): lithium
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with increased response to lithium in people with Bipolar Disorder as compared to allele T.
Article: Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics
Gene: DRD2
Variant/haplotype: rs1076560
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AC is associated with increased response to olanzapine in people with Schizophrenia as compared to genotype CC.
Notes: The associations were evaluated in conjunction with rs6314 in the HTR2A gene. rs1076560 GT/rs6314 CC diplotype was associated with better responses to antipsychotics than the rs1076560 GG/rs6314 CT diplotype
Article: Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation: A multicentre prospective cohort study
Gene: NCMAP
Variant/haplotype: rs4553122
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: Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia
Gene: HTR2A
Variant/haplotype: rs6314
Drug(s): clozapine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with increased clinical benefit to clozapine in people with Schizophrenia as compared to genotype GG.
Notes: Alleles complemented. "When investigating whether the psychopathology scales were different in carriers of HTR2A rs6314 allele, we observed several significant associations with the scores on PANSS-positive (p = 0.013). Specifically, the allele T (mutant variant) was associated with greater reduction in positive symptoms scores that could be related with better response. Only one patient presented the T/T (Tyr452/Tyr452) genotype and there were 14 patients with C/T (His452/Tyr452) heterozygosity. Those with the C/T genotype showed lower values on the scales of psychotic symptomatology compared to the C/C (His452/His452) homozygotes patients (p = 0.051)."
Article: Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizers and intermediate metabolizers
Drug(s): fentanyl, meperidine, midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 poor metabolizers and intermediate metabolizers is associated with decreased dose of fentanyl, meperidine or midazolam in people with sedation as compared to CYP2C19 normal metabolizer.
Notes: "Patients were divided into two groups based on sedation requirements during endoscopy (high vs. normal sedation). The high sedation requirement group was defined by a sedation requirement of midazolam >10 mg, fentanyl >100 mcg, meperidine >100 mg, or an aborted procedure due to failed moderate sedation and/or the transition to propofol sedation to complete the procedure. The normal sedation requirement group was defined as the complete absence of the above conditions that define the high sedation requirement group." "Patients with reduced CYP2C19 metabolism (poor + intermediate metabolizers) (OR = 0.38, 95% CI: 0.16–0.91, p = 0.03), poor CYP3A5 metabolism (OR = 0.25, 95% CI: 0.095–0.65, p = 0.0046), and poor UGT1A1 (OR = 2.76, 95% CI: 1.07–7.13, p = 0.08) had higher odds of requiring normal sedation compared to those with CYP2C19 increased metabolism, CYP3A5 intermediate metabolism, and UGT1A1 intermediate metabolism"
Article: CYP2C9*1B Promoter Polymorphisms, in Linkage with CYP2C19*2, Affect Phenytoin Autoinduction of Clearance and Maintenance Dose
Gene: CYP2C9
Variant/haplotype: rs12782374
Drug(s): warfarin
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Allele A is not associated with dose of warfarin in people with stable INRs in target range of 2-3 as compared to allele G.
Notes: after excluding those patients carrying CYP2C9*2, *3, and VKORC1 variant; alleles.
Article: Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients
Gene: MMP9
Variant/haplotype: rs2236416
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to bevacizumab in women with Breast Neoplasms as compared to allele A.
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: rs10735239
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to antiepileptics in people with Epilepsy, Generalized as compared to allele T.
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).
Article: CYP3A5 Gene Variation Influences both Systemic and Intrarenal Tacrolimus Disposition
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with increased clearance of tacrolimus in healthy individuals as compared to genotype CC.
Notes: Healthy individuals with the CT or TT (CYP3A5 *1/*3 or *1/*1) genotype had 1.6-fold higher oral tacrolimus clearance and 2.0 - 2.7-fold higher metabolite/parent area under the curve (AUC) ratios for 31-desmethyl tacrolimus (31-DMT), 12-hydroxytacrolimus, and 13-desmethyl tacrolimus (13-DMT), as compared to individuals with the CC (*3/*3) genotype. Subjects who carry two copies of loss-of-function CYP3A5 alleles (CYP3A5*3, CYP3A5*6/rs10264272 or CYP3A5*7/rs41303343) were pooled together as CYP3A5 non-expressors for this analysis. CYP3A5 *1 allele carriers were pooled togethers as CYP3A5 expressors.