shlokn/autogkb huggingface dataset:
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: rs1024323
Drug(s): metoprolol
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with decreased response to metoprolol in women with hypertensive nephrosclerosis as compared to genotype TT.
Notes: This effect was only statistically significant in men, even when stratifying for rs2960306 genotype. Response was measured by time to reach a mean arterial pressure of < or = 107 mm Hg.
Article: Genetic polymorphisms to identify patients with an optimal response to tildrakizumab in psoriasis patients from real‐life clinical practice
Gene: ATG5
Variant/haplotype: rs9373839
Drug(s): tildrakizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CT is associated with decreased clinical benefit to tildrakizumab in people with Psoriasis as compared to genotypes CC + TT.
Notes: "Our data also suggest that patients carrying the genotype GG for rs610604 (TNFAIP3), CTGT/− for rs72167053 (PDE4D) and CT for rs9373839 (ATG5) had a higher probability to not achieve PASI ≤1 after 12 months of tildrakizumab treatment, while those with CT for rs708567 (IL17RC) have a higher chance to have an optimal response to this treatment."
Article: Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): voriconazole
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: CYP2C19 *1/*17 (assigned as ultrarapid metabolizer phenotype) is not associated with dose-adjusted trough concentrations of voriconazole in children with Neoplasms as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: No significant difference in trough concentrations (adjusted for daily dose) was observed. 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: Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of warfarin in children as compared to genotype CC.
Notes: Children with at least one variant VKORC1 allele required significantly decreased doses as compared with wild type patients. Weekly maintenance doses in wild type patients (CC) were significantly higher (32 mg) than heterozygotes (CT) (23 mg) and individuals with two variant alleles (TT) (10.6 mg). In a multivariate analysis VKORC1 genotype accounted for 18.2% of the interindividual variability observed with warfarin dose. Alleles have been complemented to the plus chromosomal strand.
Article: Effect of GSTA1 Variants on Busulfan-Based Conditioning Regimen Prior to Allogenic Hematopoietic Stem-Cell Transplantation in Pediatric Asians
Gene: GSTA1
Variant/haplotype: rs3957356
Drug(s): busulfan
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased clearance of busulfan in children with hematopoietic stem cell transplantation as compared to allele C.
Notes: Alleles complemented. "The carriers of the variant allele GSTA1*B had a lower CL, which in turn reduced the elimination of busulfan; this was associated with increased AUC." There are two variants C-69T (rs3957357) and G-52A (rs3957356) which combine to form *A and *B alleles where -69C, -52G, designated as GSTA1*A; -69T, -52A, designated as GSTA1*B.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: MYT1L
Variant/haplotype: rs79663562
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with decreased response to allopurinol as compared to allele T.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2
Gene: IAPP, SLCO1A2
Variant/haplotype: rs11045995
Drug(s): rocuronium
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with decreased dose of rocuronium in women as compared to genotypes CT + TT.
Notes: Please note that alleles have been complemented to the positive strand. Although this association is significant on its own, the authors state that the decrease in dosage requirements is best explained by the combination of the CC genotype at this position with the CC genotype at rs7967354.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DDC
Variant/haplotype: rs11575553
Drug(s): heroin
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to heroin as compared to allele G.
Notes: No significant association between this variant and strength of euphoria on first heroin use.
Article: Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of warfarin in people with venous thromboembolism as compared to genotype CC.
Notes: CYP2C9 and VKORC1 variants are analyzed together to divide patients into three warfarin sensitivity types (normal, sensitive and highly sensitive). "Warfarin sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time over-anticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252)."
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: rs1153702
Drug(s): fentanyl
Phenotype category: Dosage
Significant: no
Association: Allele C is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele T.
Article: Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE
Gene: CYP2C8
Variant/haplotype: rs10882521
Drug(s): desethylchloroquine, hydroxychloroquine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased concentrations of desethylchloroquine or hydroxychloroquine in people with Lupus Erythematosus, Systemic as compared to allele G.
Notes: "The T allele of CYP2C8 (rs10882521) was related to lower HCQ (p=0.009) and DCQ (p=0.008). "
Article: Fixed dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer
Gene: CES2
Variant/haplotype: rs11075646
Drug(s): capecitabine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of capecitabine in people with Breast Neoplasms as compared to allele G.
Notes: No significant differences in the area under the concentration-time curve from 0 to infinity (AUCinf) were seen between any of the genotypes (CC, CG, GG). Nor were any significant differences seen between these genotypes when considering the capecitabine metabolites 5'-DFCR, 5'-DFUR or 5'FU (5'-fluorouracil).
Article: Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): fluindione
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with dose of fluindione in children as compared to genotype CC.
Article: Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study
Variant/haplotype: rs79663003
Drug(s): lithium
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to lithium in people with Bipolar Disorder as compared to allele C.
Notes: Patients had been taking lithium for at least 6 mo. Response to lithium was assayed using the Alda scale, which quantifies symptom improvement over time. The scale is from 0-10, with 10 being the highest response score and 0 being the lowest. The authors evaluated response using a dichotomous (=7 is "responder" and < 7 is "non-responder") and a continuous phenotype (0-10). This SNP was found to be associated with improved response to lithium using the continuous phenotype but not the dichotomous phenotype measure. The association was confirmed in an independent prospective study of 73 patients. This is one of four SNPs in LD that show association (rs79663003, rs78015114, rs74795342, rs75222709).
Article: Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A4 *1/*22 is associated with decreased clearance of midazolam in people with Kidney Transplantation as compared to CYP3A4 *1/*1.
Notes: Correcting for methylprednisone dose and type of calcineurin inhibitor (i.e. tacrolimus or cyclosporine).
Article: Clinical Impact of Cytochrome P450 2C19 Genotype on the Treatment of Invasive Aspergillosis under Routine Therapeutic Drug Monitoring of Voriconazole in a Korean Population
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 + *1/*3 (assigned as intermediate metabolizer phenotype) is associated with increased trough concentration of voriconazole in people with Hematologic Diseases and Infection as compared to CYP2C19 *1/*1 + *1/*17 (assigned as normal metabolizer phenotype) .
Notes: Heterozygous extensive (*1/*2, *1/*3) metabolizers had increased trough levels of voriconazole as compared to extensive (*1/*1, *1/*17) metabolizers. The initial voriconazole trough concentrations were 1.8, 2.7, 3.2 mg/L in EM, HEM, and PM, respectively. There was no significant difference when comparing all 3 groups however (p=0.068).
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs1381376
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele C.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy. Note that this is a A/C/G/T SNP. Based on allele frequencies reported by dbSNP, it is assumed that the major allele in this study is C and the minor allele is A. Please note that alleles have been complemented to the positive strand.
Article: Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with decreased dose-adjusted trough concentrations of tacrolimus in children with Kidney Transplantation as compared to genotype CC.
Notes: Note that this was only significant in children taking tacrolimus in twice-daily formulation (Prograf), no significant results were seen for children taking tacrolimus in  once-daily formulation (Advagraf; p=0.1). Additionally, no significant results were seen when considering dose-adjusted 0-24 hour area under the tacrolimus concentration-time curve for twice-daily or once-daily formulations (AUC0-24/dose; p=0.07, p=0.1) or dose-adjusted maximum whole-blood tacrolimus concentration for twice-daily or once-daily formulations (Cmax/dose; p=0.54, p=0.28).
Article: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Variant/haplotype: rs7802493
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: Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4‐hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus
Gene: CYP2B6
Variant/haplotype: rs4803419
Drug(s): cyclophosphamide
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with metabolism of cyclophosphamide in people with as compared to allele C.
Notes: This SNP had a small effect on cyclophosphamide (CPA) metabolite plasma concentrations (4-OH-CPA), but did not reach significance (Bonferroni corrected p-value= 0.0056).
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 TT is associated with decreased clearance of efavirenz in people with HIV Infections as compared to genotype GT.
Notes: Patients with the TT 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 8.78 mg/L [4.77-10.00] for TT genotype; P=0.005.
Article: Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?
Gene: CYP3A5
Variant/haplotype: CYP3A5 poor metabolizer
Drug(s): fentanyl, meperidine, midazolam
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 poor metabolizer is associated with decreased dose of fentanyl, meperidine or midazolam in people with sedation as compared to CYP3A5 intermediate 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: The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Gene: CSMD2
Variant/haplotype: rs506546
Drug(s): Selective serotonin reuptake inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to Selective serotonin reuptake inhibitors in people with Depressive Disorder, Major as compared to allele C.
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: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AG + GG are not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.
Notes: There is no association between selected SNPs and methotrexate plasma level at 48 h between the first dose of methotrexate infusion. med. MTX concentration: GG+AG (0.45 (0.09–41.63)) vs. AA (0.37 (0.12–3.91)). Please note: alleles have been complemented to the + chromosomal strand.
Article: Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate
Gene: GRIN2B
Variant/haplotype: rs2160734
Drug(s): acamprosate
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to acamprosate in people with Alcoholism as compared to allele T.
Notes: Tag SNPs (518 total) were selected within genes associated with alcoholism as well as genes encoding enzymes involved in glycine metabolism, glycine transporters, subunits of glycine receptors, NMDA receptors, genes involved in glutamate reuptake, synthesis or degradation and genes with reported associations with acamprosate treatment outcomes in human or animal studies. The length of time to first alcohol use “survival analysis method” was used to examine associations between clinical variables and genetic markers with efficacy of acomprasate (its ability to length  the duration of abstinence from alcohol).  The analyses were replicated in a subset of 110 participants from PREDICT, a double-blind randomized controlled trial that compared treatment outcomes including length of abstinence among alcohol- dependent subjects of German descent recruited from inpatient facilities and treated with acamprosate, naltrexone or placebo for 3 months.
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: ILKAP
Variant/haplotype: rs113095083
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele T.
Notes: The SNP was discovered in two independent cohorts, although no SNPs reached genome wide significance. The authors then considered P<1 x10^-5 as a threshold for significance (based on the results from a Q-Q plot distribution reference line). Using this revised threshold the authors reported that this SNP was associated with a lower decrease in diastolic blood pressure after hydrochlorothiazide treatment.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: HTR3A
Variant/haplotype: rs1176713
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to risperidone in people with Schizophrenia as compared to allele A.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with decreased concentrations of tacrolimus in people with Liver transplantation as compared to genotype CC.
Notes: Alleles complemented. This was seen for both donor and recipient: For donor "Among CYP3A5 rs776746 carriers, those with AA/AG genotypes have been observed to have lower Tac C/D ratios than GG genotype carriers at weeks 1, 2, 3, 4 (p = 0.005, 0.007, 0.002, <0.001, respectively)" "Tac C/D ratios of recipient CYP3A5 rs776746 AA/AG carriers were significantly lower than GG carriers at all investigated time points (p = 0.001, 0.006, 0.005, 0.003, respectively)."
Article: Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma
Gene: OR2B11
Variant/haplotype: rs35305980
Drug(s): axitinib
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with concentrations of axitinib in people with Carcinoma, Renal Cell as compared to allele del.
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: NUDT15 R139C Variants Increase the Risk of Azathioprine-Induced Leukopenia in Chinese Autoimmune Patients
Gene: TPMT
Variant/haplotype: rs1142345
Drug(s): thioguanine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with concentrations of thioguanine in people with Autoimmune Diseases, Lupus Erythematosus, Systemic and Sjogren's Syndrome as compared to allele T.
Notes: after treatment with azathioprine and 6-TGN was not significantly different between patients with leukopenia or the controls.
Article: Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*46
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *1/*46 is associated with decreased dose of warfarin.
Notes: in a case study.
Article: Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of methadone in people with Opioid-Related Disorders as compared to allele G.
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.
Article: The Effect of CYP2D6 polymorphisms on the Response to Pain Treatment for Pediatric Sickle Cell Pain Crisis
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*40
Drug(s): codeine
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 *40 is associated with decreased response to codeine in children with Anemia, Sickle Cell as compared to CYP2D6 *1.
Notes: Pediatric patients with severe sickle cell disease who have failed codeine therapy for a pain crisis while taking hydroxyurea were found to be more likely to have a reduced function allele (including *4, *5, *6, *17, *40) as compared to those with mild disease, likely due to a decreased conversion of codeine to morphine. Allele frequencies were not reported. Reduced function alleles were grouped for analysis.