shlokn/autogkb huggingface dataset:
Article: ABC Transporter Polymorphisms are Associated with Irinotecan Pharmacokinetics and Neutropenia
Gene: ABCB1
Variant/haplotype: rs12720066
Drug(s): SN-38
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AC + CC are associated with decreased exposure to SN-38 in people with Colorectal Neoplasms as compared to genotype AA.
Notes: AUC of SN-38 was adjusted for irinotecan dose.
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: rs17577
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bevacizumab in women with Breast Neoplasms as compared to allele G.
Notes: Listed as rs2274756 in paper.
Article: Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance
Gene: NR1I2
Variant/haplotype: rs1523130
Drug(s): donepezil
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with clearance of donepezil in people with Alzheimer Disease as compared to genotype TT.
Notes: Genotypes of CC, CT and TT did not influence donepezil clearance in a covariate model.
Article: CYP2D6 genotypes, endoxifen levels, and disease recurrence in 224 Filipino and Vietnamese women receiving adjuvant tamoxifen for operable breast cancer
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*5, CYP2D6*10, CYP2D6*41
Drug(s): 4-hydroxytamoxifen, N-desmethyltamoxifen, tamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 *10/*10 + *10/*41 + *1/*5 + *2/*5 + *5/*10 are not associated with decreased concentrations of 4-hydroxytamoxifen, n-desmethyltamoxifen and tamoxifen in women with Breast Neoplasms as compared to CYP2D6 *1/*1 + *1/*2 + *2/*2.
Notes: No information on menopausal status or if tamoxifen only treatment. No co-treatment with CYP2D6 inhibitors CYP2D6 alleles *2, *3, *4, *5, *6, *10, and *41 are genotyped with predeveloped TaqMan Genotyping Assays. Genotypes were categorized as normal (fully functional CYP2D6 alleles: *1 and *2 -*1/*1, *1/*2, *2/*2), intermediate (alleles associated with reduced enzyme activity: heterozygous for *10 and *41-*1/*10, *2/*10, *1/*41), and slow (homozygous for *10, *41 variants and one or more non-functional null alleles: *3-*6-*10/*10, *10/*41, *1/*5, *2/*5, *5/*10). [pre-menopausal][post-menopausal] [adjuvant]  [DNA source: leukocytes] [HWE: Vietnamese *1, 2, 4, 5, 10, 41 yes Filipino *1 and *2 no rest yes]
Article: Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics
Gene: UGT1A3
Variant/haplotype: UGT1A3*1, UGT1A3*2
Drug(s): montelukast
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A3 *2 is associated with decreased concentrations of montelukast in healthy individuals as compared to UGT1A3 *1/*1.
Notes: The UGT1A3*2 is associated with reduced area under the plasma concentration-time curve (AUC) of montelukast (17% reduction per copy of each allele, P=2.99 × 10-10). This allele is strongly associated with increased UGT1A3 expression in vitro.
Article: Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study
Gene: GLA
Variant/haplotype: rs398123223
Drug(s): migalastat
Phenotype category: Efficacy
Significant: not stated
Association: Allele G is associated with increased response to migalastat in people with Fabry Disease.
Notes: Patients carrying the G allele showed improvements in renal function, cardiac geometry (specifically, reductions in left ventricular mass index) and gastrointestinal symptoms as well as reductions in GL-3 inclusions and plasma lyso-Gb3 and an increase in PBMC alpha-Gal A activity when treated with migalastat. Clinical benefit of migalastat was not substantially affected by disease severity. This variant was designated as an 'amenable variant' to migalastat treatment following an in vitro assay where migalastat increased the activity of alpha-Gal A by at least 3%. As all data were derived from post hoc analysis, statistical analyses were not carried out. Variant referred to as Leu300Pro in the paper.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DBH
Variant/haplotype: rs129915
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of methadone in people with Heroin Dependence as compared to allele A.
Article: Impact of NFIB and CYP1A variants on clozapine serum concentration—A retrospective naturalistic cohort study on 526 patients with known smoking habits
Gene: NFIB
Variant/haplotype: rs28379954
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype CT is associated with decreased dose-adjusted trough concentrations of clozapine as compared to genotype TT.
Notes: significance is only given for combination of both CYP1A rs2472297 C>T and NFIB rs28379954 T>C genotypes
Article: Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population
Gene: CYP4F2
Variant/haplotype: rs2189784
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of warfarin as compared to allele G.
Notes: Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms.
Article: IL28B polymorphisms associated with therapy response in Chilean chronic hepatitis C patients
Gene: IFNL3
Variant/haplotype: rs8099917
Drug(s): peginterferon alfa-2a, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased response to peginterferon alfa-2a and ribavirin in people with Hepatitis C, Chronic as compared to genotypes GT + TT.
Notes: This genotype is associated with sustained virological response (SVR).
Article: UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): irinotecan
Phenotype category: Efficacy
Significant: no
Association: UGT1A1 *1/*28 + *28/*28 are not associated with response to irinotecan in people with Colorectal Neoplasms as compared to UGT1A1 *1/*1.
Notes: Clinical response - when a patient had either a complete or a partial remission.
Article: Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD
Gene: COMT
Variant/haplotype: rs4680
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AA + AG.
Notes: The A allele and G allele are reported in the paper as the Val allele and Met allele respectively.
Article: Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients
Gene: C18orf56, TYMS
Variant/haplotype: rs45445694
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Genotype (CCGCGCCACTTCGCCTGCCTCCGTCCCG)3 is not associated with response to methotrexate in people with Arthritis, Rheumatoid.
Article: OPRM1, OPRK1 and COMT Genetic Polymorphisms Associated with Opioid Effects on Experimental Pain: A Randomized, Double-Blind, Placebo-Controlled Study
Gene: OPRK1
Variant/haplotype: rs702764
Drug(s): butorphanol
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is associated with increased response to butorphanol in healthy individuals as compared to genotypes CT + TT.
Notes: Nominally significant difference in heat pain threshold between genotype groups, but this association was not seen in other pain modalities. Study-wide significance was set to p<0.017.
Article: GENETIC VARIATION IN CYP4A11 AND BLOOD PRESSURE RESPONSE TO MINERALOCORTICOID RECEPTOR ANTAGONISM OR ENAC INHIBITION: AN EXPLORATORY PILOT STUDY IN AFRICAN AMERICANS
Gene: CYP4A11
Variant/haplotype: rs1126742
Drug(s): amiloride, spironolactone
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to amiloride or spironolactone in people with Hypertension as compared to genotypes AA + AG.
Notes: Please note that alleles have been complemented to the positive strand. An expected increase in aldosterone levels in response to treatment was not seen in patients with the GG genotype. This variant was in complete disequilibrium with rs3890011.
Article: Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy
Gene: SLC22A4
Variant/haplotype: rs1050152
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotypes CC + CT.
Notes: This genotype was not significantly with associated with likelihood of achieving major cytogenetic response (MCgR) within 12 months. MCgR was defined as achieving either a complete or partial cytogenetic response (CCgR; PCgR). Cytogenetic response was based on bone marrow assessment, where CCgR was 0% Ph+ cells, and PCgR was >0 to 35% Ph+ cells.
Article: Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate
Gene: CYP3A4
Variant/haplotype: CYP3A4 poor metabolizers and intermediate metabolizers
Drug(s): buprenorphine, methadone
Phenotype category: Efficacy
Significant: no
Association: CYP3A4 intermediate metabolizer and poor metabolizer is not associated with response to buprenorphine or methadone in people with Opioid-Related Disorders as compared to CYP3A4 normal metabolizer.
Notes: Response defined by changes in the rate of dropout from treatment between metabolizer phenotypes. Study genotyped for the CYP3A4 *1, *13, *15A and *22 alleles and then assigned metabolizer phenotypes.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Variant/haplotype: rs3002142
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with trough concentration of vancomycin as compared to allele T.
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: SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): atorvastatin
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CT is not associated with response to atorvastatin in people with Hypercholesterolemia as compared to genotype TT.
Notes: No significant differences in percent change between the genotypes for total cholesterol (p=0.58), high-density lipoprotein cholesterol (HDL-C; p=0.15), low-density lipoprotein cholesterol (LDL-C; p=0.34) or triglycerides (p=0.92). Patients were treated with atorvastatin for 4 weeks at 10 mg/day.
Article: VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide
Gene: VEGFA
Variant/haplotype: rs3025039
Drug(s): cyclophosphamide
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to cyclophosphamide in people with Prostatic Neoplasms as compared to genotypes CC + CT.
Notes: No significant difference genotype frequencies were seen between patients who were responders to chemotherapy, and those who were non-responders. Patients with advanced prostate cancer undergoing metronomic chemotherapy. Responders were classified as patients who had a decrease in prostrate-specific antigen (PSA) of >= 50% and a PSA stabilization of >= 6 months. Patients also received celecoxib and dexamethasone, and some patients received docetaxel-, mitoxantrone-, and vinorelbine-based chemotherapeutic regimens.
Article: Association of HTR1A Gene Polymorphisms with Efficacy and Plasma Concentrations of Atypical Antipsychotics in the Treatment of Male Patients with Schizophrenia
Gene: HTR1A
Variant/haplotype: rs10042486
Drug(s): quetiapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of quetiapine in men with Schizophrenia as compared to genotype CT.
Notes: "Plasma concentrations of the TT genotype at rs10042486 locus were significantly higher than those of the CT genotype at postrandomized week 6 (t = 3.126, P = 0.005)."
Article: Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype
Gene: CYP2B6
Variant/haplotype: CYP2B6 poor metabolizer
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 poor metabolizer is associated with increased exposure to efavirenz in infants as compared to CYP2B6 normal metabolizer and intermediate metabolizer.
Notes: "Efavirenz newborn concentration varies based on both CYP2B6 516 G>T (rs3745274) and CYP2B6 983 T>C (rs28399499) newborn genotype (Table 3). The median (IQR) efavirenz DBS concentration in newborn stratified as fast (CYP2B6 516 GG, n = 25), intermediate (CYP2B6 516 GT, n = 36), and slow metabolizers (CYP2B6 516 TT, n = 19). 17.4 h after maternal dose were 999.7 ng/ml (744–1285), 1240 ng/ml (709–1984), and 1792 ng/ml (1201–3188), respectively. Similarly, newborn efavirenz DBS concentration varied based on maternal CYP2B6 genotypes: fast metabolizers (n = 26), 747 ng/ml (602–1060); intermediate metabolizers (n = 50), 1177 (898–1765); and slow metabolizers (n = 14), 3094 (2126 3812). Additionally, we observed a genotype effect on efavirenz concentrations in newborns when stratified by CYP2B6 genotype within each maternal reference group (fast, intermediate, and slow). Newborns with a slow metabolizer status, born to mothers with intermediate or slow metabolizer statuses, had higher efavirenz plasma exposure."
Article: An Investigational Study on the Role of CYP2D6, CYP3A4 and UGTs Genetic Variation on Fesoterodine Pharmacokinetics in Young Healthy Volunteers
Gene: CYP2D6
Variant/haplotype: CYP2D6 ultrarapid metabolizer
Drug(s): fesoterodine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 ultrarapid metabolizer is associated with increased clearance of fesoterodine in healthy individuals as compared to CYP2D6 normal metabolizer and intermediate metabolizer and poor metabolizer.
Notes: "Lastly, Cl/F was significantly higher in the CYP2D6 UMs compared to the NMs and IMs/PMs (puv = 0.008 and puv < 0.001, respectively; β = −0.131, R2 =0.409, pmv = 0.001) and lower in the CYP2D6 IMs/PMs compared to the NMs (puv = 0.005) (Table 3)." The 21 SNPs for CYP2D6 measured are listed in table 5 and methods states that "deletion (*5), duplication, and the presence of hybrid structures were analyzed".
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: rs2236257
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 G.
Notes: This SNP was not significantly associated with compliance with methadone maintenance therapy or 'negative rate of morphine urine test'.
Article: G-Protein-Coupled Receptor Kinase 4 Polymorphisms and Blood Pressure Response to Metoprolol Among African Americans: Sex-Specificity and Interactions
Gene: GRK4
Variant/haplotype: rs2960306
Drug(s): metoprolol
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GT + TT are associated with decreased response to metoprolol in men with hypertensive nephrosclerosis.
Notes: in cox regression analysis when examining the rs1024323 genotype (variant interaction analysis - no association was found examining this variant on its own). Response was measured by time to reach a mean arterial pressure of < or = 107 mm Hg.
Article: Determination of the Most Influential Sources of Variability in Tacrolimus Trough Blood Concentrations in Adult Liver Transplant Recipients: A Bottom-Up Approach
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AG + GG is associated with increased clearance of tacrolimus in people with liver transplantation as compared to genotype AA.
Notes: There was a significant difference in the mean apparent clearance between the three different genotypes. Please note alleles have been complemented to the plus chromosomal strand.
Article: Association of Common C-Reactive Protein (CRP) Gene Polymorphisms With Baseline Plasma CRP Levels and Fenofibrate Response
Gene: CRP
Variant/haplotype: rs3091244
Drug(s): fenofibrate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GG + GT are associated with increased response to fenofibrate in people with Metabolic Syndrome as compared to genotypes AA + AT.
Notes: Patients with the GG, GA and GT genotypes had a greater reduction in C-reactive protein (CRP) levels between baseline and 3 weeks of treatment, as compared to those with the AA and AT genotypes. In strong linkage disequilibrium with rs1205 and rs1417938 (r2 = 0.4 - 0.9, p < 0.001) and rs3093059 (r2 = 0.935, p < 0.001).
Article: Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test
Gene: ATF2
Variant/haplotype: rs7583431
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to fentanyl in people with Pain, Postoperative as compared to allele C.
Notes: Increased copy number of the A allele correlated with an increase in the analgesic effect of fentanyl.
Article: ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): rivaroxaban
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased half-life time of rivaroxaban in healthy individuals as compared to genotypes GG + GT.
Notes: Alleles complemented. "In our dataset, individuals with the ABCG2 421 A/A genotype had considerably higher average values of Vd/F (508.27±72.79 L; P=0.001) and t1/2 (41.04±23.73 h; P=0.000) compared to those with the other genotypes, 421 C/A and 421 C/C, with no statistically significant difference between means." "Individuals carrying two mutant alleles in the ABCG2 SNP tended to have lower AUC, Cmax, and Cl/F (as shown in Table 4) compared to carriers of the wild-type genotype. However, it is essential to note that these differences did not achieve statistical significance (P>0.05)." This was reported for the fasting group which had 2 TT individuals, the fed group had no TT individuals.
Article: CYP2C19 polymorphisms in the Thai population and the clinical response to clopidogrel in patients with atherothrombotic-risk factors
Gene: CYP2C19
Variant/haplotype: CYP2C19*2, CYP2C19*3
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *2/*2 + *2/*3 + *3/*3 is associated with decreased response to clopidogrel in people with Cardiovascular Diseases.
Notes: Subjects with the *2/*2, *2/*3 or *3/*3 genotype had a greater likelihood of being a non-responder to clopidogrel (a platelet inhibition percentage of < 10% pre- and post-treatment) than a responder (a platelet inhibition percentage of >= 10% pre- and post-treatment).
Article: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis
Gene: LEPR, LEPROT
Variant/haplotype: rs1045895
Drug(s): apremilast
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with decreased clinical benefit to apremilast in people with Psoriasis as compared to genotype GG.
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. "Apart from the allelic association, SNP rs1045895 also shows association with the response under the dominant model of inheritance"
Article: Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma
Gene: UGT1A7
Variant/haplotype: rs17868323
Drug(s): axitinib
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele G is associated with concentrations of axitinib in people with Carcinoma, Renal Cell as compared to allele T.
Notes: The authors develop a prediction model and calculated area under the concentration curve (AUC) using 6 SNPs (rs17868323, rs3832043, rs2231142, rs2032582, rs1045642, rs35305980) was compared with actual AUC in 16 patients prospectively which significantly correlated with the objective response rate (P = 0.0002), hand-foot syndrome, P = 0.0055 and hypothyroidism, P = 0.0381, and correlated with actual AUC (P < 0.0001) - the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066).
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs10512361
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele T.
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). Please note, alleles have been complemented to the + chromosomal strand.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: MIA3
Variant/haplotype: rs1053316
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of vancomycin as compared to allele G.
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: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: TH
Variant/haplotype: rs3842727
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele T is not associated with dose of methadone in people with Heroin Dependence as compared to allele G.
Article: Intestinal CYP3A4 and Midazolam Disposition in vivo Associate with VDR Polymorphisms and Show Seasonal Variation
Gene: VDR
Variant/haplotype: rs4516035
Drug(s): midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased clearance of midazolam as compared to allele C.
Notes: TT > TC > CC.