shlokn/autogkb huggingface dataset:
Article: Verification of Pharmacogenetics-Based Warfarin Dosing Algorithms in Han-Chinese Patients Undertaking Mechanic Heart Valve Replacement
Gene: VKORC1
Variant/haplotype: rs9934438
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype AA is associated with decreased dose of warfarin in people with heart valve replacement as compared to genotypes AG + GG.
Notes: The goal of this study was to compare the accuracy of 8 different warfarin dosing algorithms, including the IWPC, and 6 Han Chinese PGx warfarin dosing algorithms, in Han Chinese patients taking warfarin scheduled to undergo mechanic heart valve replacement surgery. The authors concluded that the mean absolute error (MAE) of all algorithms was less than 0.6mg/day in initial and stable doses, and the percentage of patients whose actual doses were within 20% of their predicted dose was 45% in all algorithms.  Predictive power of algorithms was highest for patients in the ideal-dose range and lowest for patients in the low and high dose range.; The most accurate predictions came from three Han-Chinese PGx warfarin dosing algorithms (Du et al. 2010, Huang et al. 2009, Miao et al. 2007).
Article: Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins
Gene: CXCL5
Variant/haplotype: rs352046
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to hmg coa reductase inhibitors in people with Acute coronary syndrome as compared to genotypes CG + GG.
Notes: Since this is a GC SNP, there is the possibility of stranding error.  The CXCL5 gene is on the negative chromosomal strand, so I complemented the reported results, which are: GG patients on statins showed a significant, 58% relative risk reduction (p = 0.0009);GC patients on statins showed a non-significant 25% relative risk reduction(p = 0.48), and CC patients on statins showed a non-significant 39% relative risk INCREASE (p = 0.46).
Article: Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients
Gene: CYP2C9
Variant/haplotype: CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: CYP2C9 *3 is associated with dose of warfarin in people with Stroke.
Notes: This study undertook the development of a warfarin pharmacogenetic dosing algorithm and then compared it against other dosing algorithms. This variant was included in the algorithm. However, note that there was no significant difference in stable warfarin dose between patients with the *1/*1 genotype (3.8+/1.4 mg/day) and the *1/*3 genotype (2.6+/-0.5 mg/day); only 4 patients carried the *3 allele.
Article: Genetic Variation in CYP2D6, UGT1A4, SLC6A2 and SLCO1B1 Alters the Pharmacokinetics and Safety of Mirabegron
Gene: CYP2D6
Variant/haplotype: CYP2D6 intermediate metabolizer
Drug(s): mirabegron
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 intermediate metabolizer is associated with increased half-life time of mirabegron in healthy individuals as compared to CYP2D6 normal metabolizer and ultrarapid metabolizer.
Notes: "No CYP2D6 poor metabolizers (PMs) were available in this research." "A higher t1/2 was observed in CYP2D6 intermediate metabolizers (IMs) compared to ultrarapid (UMs) and normal metabolizers (NMs) (puv = 0.028). Significance was transformed into a tendency after Bonferroni post hoc tests (NMs vs. IMs, puv = 0.074, UMs vs. IMs puv = 0.124 and NMs vs. UMs puv = 0.624). However, the t1/2 remained significantly higher in IMs compared to UMs and NMs merged in a unique group (UMs + NMs) (puv = 0.018). Differences in the t1/2 were accompanied by a not significantly lower AUC/DW and Cmax/DW in CYP2D6 UMs compared to NMs and IMs."
Article: PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients
Gene: NR1I2
Variant/haplotype: rs2472677
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CC is not associated with metabolism of efavirenz in people with HIV Infections as compared to genotype TT.
Notes: Plasma levels of efavirenz were not statistically significantly different between the CC, CT, TT genotypes of this SNP.
Article: The association between serotonin-related gene polymorphisms and susceptibility and early sertraline response in patients with panic disorder
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR long form (L allele), SLC6A4 HTTLPR short form (S allele)
Drug(s): sertraline
Phenotype category: Efficacy
Significant: yes
Association: SLC6A4 HTTLPR short form (S allele) is associated with decreased response to sertraline in people with Panic Disorder as compared to SLC6A4 HTTLPR long form (L allele).
Article: Bleeding Events Associated with Rivaroxaban Therapy in Naive Patients with Nonvalvular Atrial Fibrillation: A Longitudinal Study from a Genetic Perspective with INR Follow-Up
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): rivaroxaban
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AG + GG is associated with decreased concentrations of rivaroxaban in people with Atrial Fibrillation as compared to genotype AA.
Notes: "In our study, we found that for ABCB1-related rs4148738 and rs2032582, there was a statistically significant difference between the wild and mutant genotypes and a decrease in the CDR max values of rivaroxaban, while CDRss was statistically significant between the wild and homozygous mutant genotypes. For rs1045642 and rs1128503 of ABCB1, the decreased CDR max and Css levels of rivaroxaban were statistically significant between the wild (AA) and mutant (AG, GG) genotypes. Our findings suggest that polymorphism in the P-glycoprotein expressed by the ABCB1 gene can affect the peak plasma levels of rivaroxaban."
Article: Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis
Gene: PTPN2
Variant/haplotype: rs7234029
Drug(s): adalimumab
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to adalimumab in people with Arthritis, Rheumatoid as compared to allele A.
Notes: A significant association between rs7234029 and response to adalimumab as determined by EULAR score was seen at six months after beginning treatment however this significance was lost upon correction for multiple variables. No significant association was seen at two years after beginning treatment.; No significant associations were seen at either time point when response was measured as number of patients in remission or with low disease activity.
Article: A Randomized Trial of Pharmacogenetic Warfarin Dosing in Naïve Patients with Non-Valvular Atrial Fibrillation
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele T is associated with dose of warfarin.
Notes: This study assessed whether a pharmacogenetic dosing algorithm, which included this variant as well as the CYP2C9*2, CYP2C9*3 and CYP4F2*3 variants, is superior in overall anticoagulation control when compared to clinical standard of care. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): morphine
Phenotype category: Dosage
Significant: yes
Association: Genotypes AG + GG is associated with increased dose of morphine in women with Pain, Postoperative as compared to genotype AA.
Notes: All patients were Arab women undergoing laparoscopic cholecystectomy. "Both OPRM1 (rs1799971, A>G), and rs2952768 (T>C) showed statistically significant association with IO total morphine dose requirements. Patients carrying OPRM1 minor allele (GG) and (AG) genotypes had a significantly higher total morphine mean rank compared to the AA genotype [62.9 vs 47.1"
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: TMEM205
Variant/haplotype: rs896412
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to platinum in people with Lung Neoplasms as compared to allele C.
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: Pharmacogenomics of aromatase inhibitors in postmenopausal breast cancer and additional mechanisms of anastrozole action
Gene: DLG2
Variant/haplotype: rs2449598
Drug(s): anastrozole
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to anastrozole in women with Breast Neoplasms as compared to allele G.
Notes: Response was measured by the decrease in estrogen levels over the course of treatment.
Article: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain
Gene: COMT
Variant/haplotype: rs2239393
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 of Genetic Variation in Cystathionine-β-Synthase and Arsenic Metabolism
Gene: CBS
Variant/haplotype: rs4920037
Drug(s): Arsenic compounds
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Genotypes AA + AG are associated with increased metabolism of Arsenic compounds as compared to genotype GG.
Notes: measured as as excreted monomethylarsonic acid.
Article: Comprehensive characterization of pharmacogenetic variants in TPMT and NUDT15 in children with acute lymphoblastic leukemia
Gene: TPMT
Variant/haplotype: rs12199316
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: yes
Association: Allele G is associated with increased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.
Notes: Since this is a C/G non-coding variant in gene on minus strand, confirmed with authors that the allele associated with increased dose is G as measured on plus chromosomal strand.
Article: Genome-wide association analysis of common genetic variants of resistant hypertension
Gene: PTPRD
Variant/haplotype: rs324498
Drug(s): Antihypertensives
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with decreased response to Antihypertensives in people with Hypertension as compared to allele A.
Notes: The G allele was associated with increased odds of a patient developing resistant-hypertension. Participants were classified as having resistant hypertension if their SBP was ≥140 or DBP ≥ 90 using three or more medications, or if they were using four or greater antihypertensive medications regardless of BP. However, this SNP failed to reach genome-wide significance in either the INVEST or SPS3 cohorts or when both cohorts were combined. Additionally, this association could not be validated in an eMERGE dataset.
Article: No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV‐1–Infected Subjects
Gene: CYP3A5
Variant/haplotype: CYP3A5 poor metabolizers
Drug(s): maraviroc
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 poor metabolizer is associated with increased concentrations of maraviroc in people with HIV Infections as compared to CYP3A5 normal metabolizer.
Notes: In study A4001110, black CYP3A5 poor metabolizers had a significant increase in average maraviroc plasma concentrations compared to black extensive metabolizers. The authors determined this difference in maraviroc concentrations to not be clinically significant.
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: rs6912029
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele G 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: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele G.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.
Article: The Pharmacogenetics of Tacrolimus in Corticosteroid-Sparse Pediatric and Adult Kidney Transplant Recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *1/*1 + *1/*3 is associated with trough concentration of tacrolimus in children with Kidney Transplantation as compared to CYP3A5 *3/*3.
Article: CYP2A6 and GABRA2 Gene Polymorphisms are Associated With Dexmedetomidine Drug Response
Gene: CYP2A6
Variant/haplotype: rs28399433
Drug(s): dexmedetomidine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased clearance of dexmedetomidine in women as compared to allele A.
Notes: "Female patients aged 18–60 years undergoing laparoscopic with ASA I-II [ASA I: normal healthy patients; ASA II: patients with mild systemic disease". "Dexmedetomidine was continuous intravenous infused at 1 μg/kg for 10 min before the induction period of general anesthesia.""harmacokinetic studies were performed on 99 participants, and pharmacodynamic studies were performed on all participants. All participants had 5 ml of peripheral blood sampled preoperatively for DNA isolation and genetic testing."
Article: Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks
Gene: IL1B
Variant/haplotype: rs1143634
Drug(s): aspirin, diclofenac, ibuprofen, indomethacin, ketorolac, naproxen
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with clinical benefit to aspirin, diclofenac, ibuprofen, indomethacin, ketorolac or naproxen in people with Migraine without Aura as compared to allele G.
Notes: Please note that alleles have been complemented to the positive strand.
Article: Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Genotypes CT + TT is not associated with increased dose of warfarin in people with Atrial Fibrillation, Cardiomyopathies, heart valve replacement, Peripheral Vascular Diseases, Pulmonary Embolism and Venous Thrombosis as compared to genotype CC.
Article: The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC
Gene: CES1
Variant/haplotype: rs71647871
Drug(s): dabigatran
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with decreased dose-adjusted trough concentrations of dabigatran in people with Atrial Fibrillation as compared to allele C.
Notes: Alleles complemented
Article: TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)
Gene: TCF7L2
Variant/haplotype: rs7903146
Drug(s): glipizide
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to glipizide as compared to allele C.
Notes: as measured by shorter time and a steeper slope to trough glucose levels in people with risk factors for type 2 diabetes.
Article: Two Novel Loci of RELN Associated With Antipsychotics Response in Chinese Han Population
Gene: RELN
Variant/haplotype: rs39339
Drug(s): aripiprazole, olanzapine, perphenazine, quetiapine, risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to aripiprazole, olanzapine, perphenazine, quetiapine or risperidone in people with Schizophrenia as compared to allele T.
Notes: Response was assessed by changes in PANSS score. A reduction of 50% or more in PANSS score was classified as a good response.
Article: Fc‐gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer
Gene: FCGR3A
Variant/haplotype: rs396991
Drug(s): cetuximab
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to cetuximab in people with Colorectal Neoplasms as compared to allele A.
Notes: Overall survival and progression-free survival were used as indicators of response to cetuximab.
Article: Association of Polymorphisms in Pharmacogenetic Candidate Genes with Propofol Susceptibility
Gene: HTR2A
Variant/haplotype: rs6313
Drug(s): propofol
Phenotype category: Dosage
Significant: yes
Association: Genotype AA is associated with decreased dose of propofol as compared to genotypes AG + GG.
Notes: Patients undergoing thyroid resection surgery. 46/146 of patients with the AA genotype had higher effect-site concentration (Cep) values  for propofol (1.85±0.96 µg/ml) versus the100/146 patients  with the GA+GG genotypes (1.53±0.76µg/ml). The AA genotype was also associated with longer onset times of propofol induction (3.12±2.68min) versus the GA+GG genotypes (2.19±1.53min). The G allele was also associated with less propofol and less time for propofol to induce anesthesia. Please note: the authors examined 58 SNPs but did not do multiple testing corrections.
Article: Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters
Gene: EPHX1
Variant/haplotype: rs1051740
Drug(s): phenprocoumon
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotype CC is associated with decreased dose of phenprocoumon as compared to genotypes CT + TT.
Notes: Patients with the CC genotype require significantly lower daily doses of phenprocoumon as compared to patients with the CT or TT genotype. While it seems that there may be a gene dose effect (TT>CT>CC), the paper did not specify whether or not this is the case. Daily dose is also negatively correlated with age. This study published an algorithm for daily dose that includes height, although height was not significant in univariate analysis. This SNP is not associated with differences in phenprocoumon concentration.
Article: Pharmacogenetic study of seven polymorphisms in three nicotinic acetylcholine receptor subunits in smoking-cessation therapies
Gene: CHRNA3, CHRNA5
Variant/haplotype: rs16969968
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to bupropion, nicotine and varenicline in people with Tobacco Use Disorder as compared to allele G.
Notes: Authors looked at the effect of variants on response to the smoking cessation therapies varenicline, bupropion and nicotine replacement therapy.; Please note that alleles have been complemented to the positive strand.
Article: Influence of NAT2 Polymorphisms on Sulfamethoxazole Pharmacokinetics in Renal Transplant Recipients
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): sulfamethoxazole
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AC is not associated with metabolism of sulfamethoxazole in people with Kidney Transplantation as compared to genotype AA.
Notes: CYP2C9 *1/*3 and *1/*1 genotypes were compared, and no significant difference in plasma sulfamethoxazole AUC (0-24hr) was seen.
Article: Significance of CYP3A4∗1G and OPRM1 A118G Polymorphisms in Postoperative Sufentanil Analgesia in Women of Different Ethnicities
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): sufentanil
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of sufentanil in women with Pain, Postoperative as compared to allele G.
Article: Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia
Gene: FPGS
Variant/haplotype: rs1544105
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CC + CT.
Notes: Please note that alleles have been complemented to the positive strand. This association was only significant at the 24 hour timepoint.
Article: µ-Opioid Receptor Gene (OPRM1) Polymorphism A118G: Lack of Association in Finnish Populations with Alcohol Dependence or Alcohol Consumption
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of ethanol as compared to allele A.
Notes: No significant association between this variant and alcohol consumption.
Article: Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease
Gene: TLN1
Variant/haplotype: rs10814270
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with increased resistance to clopidogrel in people with Coronary Disease as compared to allele C.
Article: No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients
Gene: SLC22A1
Variant/haplotype: rs12208357
Drug(s): morphine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with exposure to morphine in people with Pain, Postoperative as compared to allele C.
Notes: Analyzed as part of haplotypes with rs34059508, rs72552763 and rs34130495. There was a non-significant trend for patients carrying reduced function alleles to have increased exposure to morphine, but the change in exposure is not large enough to be of clinical importance.