shlokn/autogkb huggingface dataset:
Article: TET2 and CSMD1genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives
Gene: TET2
Variant/haplotype: rs12505746
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with decreased response to hydrochlorothiazide in people with Essential hypertension as compared to allele G.
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 systolic blood pressure after hydrochlorothiazide treatment.
Article: Effect of UGT2B10, UGT2B17, FMO3, and OCT2 Genetic Variation on Nicotine and Cotinine Pharmacokinetics and Smoking in African Americans
Gene: FMO3
Variant/haplotype: rs2266782
Drug(s): cotinine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with metabolism of cotinine in people with Tobacco Use Disorder as compared to allele A.
Notes: This SNP is not associated with the pharmacokinetic measures of cotinine. Measures include half-life, Cmax, AUC, non renal clearance, and total clearance.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: ABCG2
Variant/haplotype: rs10011796
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to allopurinol as compared to allele C.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: ABCG2
Variant/haplotype: rs4148157
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with decreased response to allopurinol as compared to allele G.
Notes: Response to allopurinol was determined by whether serum uric acid concentrations decreased following allopurinol treatment.
Article: Warfarin Dosage Response Related Pharmacogenetics in Chinese Population
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased concentrations of warfarin in people with as compared to genotype CT.
Notes: 130 plasma samples were obtained 12 hours after the last dose of warfarin. The plasma warfarin concentrations of these samples were comparing plasma concentration within the group of patients with INR between 1.5–2.5 (n = 92) between genotype groups. rs9923231 was associated with a significant reduction of warfarin plasma concentration ( genotype AA 1117.29±323.23 ng/ml vs genotype AG 1675.73±431.09 ng/ml, p < 0.001). rs9923231 was not included in the multiple linear regression analysis because of collinearity. Patients were grouped according to INR and genotypes and those with the G allele needed a higher plasma concentration to achieve the similar goal INR.
Article: Association of variants in NEDD4L with blood pressure response and adverse cardiovascular outcomes in hypertensive patients treated with thiazide diuretics
Gene: NEDD4L
Variant/haplotype: rs1008899
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to hydrochlorothiazide in people with Hypertension as compared to allele G.
Article: VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People
Gene: CYP4F11
Variant/haplotype: rs8104361
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of warfarin as compared to allele G.
Notes: in Alaska Native and American Indian People.
Article: Assessing the Contribution of Opioid- and Dopamine-Related Genetic Polymorphisms to the Abuse Liability of Oxycodone
Gene: OPRK1
Variant/haplotype: rs963549
Drug(s): oxycodone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to oxycodone as compared to allele C.
Notes: No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test, subjective effects of oxycodone.
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: SLC19A1
Variant/haplotype: rs3788200
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: AG+GG (0.45 (0.09–41.63)) vs. AA (0.47 (0.11–34.05)).
Article: Effect of Genetic Variability in the CYP4F2, CYP4F11, and CYP4F12 Genes on Liver mRNA Levels and Warfarin Response
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with increased dose of warfarin as compared to allele C.
Notes: The T allele was associated with increased stable dose (mg/day) of warfarin and explained 4.3% of the variance in dose. CC=3.7±0.1 CT=4.3±0.2 TT=5.3±0.4. The addition of rs2108622 to PGx algorithm (included CYP2C9, VKORC1) explained a further 0.5–0.7% of variability. When conditioned on rs7248867, the association w/ rs2108622 & warfarin dose decreased (beta initial = 0.078, beta conditional = 0.065, initial P-value = 0.003, conditional P-value = 0.015). When conditioned on rs2074568, decrease of magnitude and significance also rs2108622 (beta conditional = 0.069, conditional P-value= 0.009). Suggests that rs7248867 and rs2074568 are correlated with rs2108622.
Article: Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis
Gene: KCNJ11
Variant/haplotype: rs2285676
Drug(s): sitagliptin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to sitagliptin in people with Diabetes Mellitus, Type 2.
Notes: "For KCNJ11 gene polymorphisms, patients with the rs2285676 CC genotype in the study group had a median HbA1c improvement of 1.02 (IQR, 0.90–1.22), while the control group showed 1.31 (IQR, 1.08–1.42; P < .001), indicating more substantial insulin secretion capability with sitagliptin."
Article: Individual and combined associations of genetic variants in CYP3A4, CYP3A5, and SLCO1B1 with simvastatin and simvastatin acid plasma concentrations
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): simvastatin, simvastatin acid
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 *3 is not associated with concentrations of simvastatin or simvastatin acid in people with Hypercholesterolemia as compared to CYP3A5 *1.
Notes: Patients were followed for 6 weeks (40 mg simvastatin at bedtime) and seen at the clinic at 2 week intervals.
Article: The genetics of cardiac failure: Role of a G protein-coupled receptor polymorphism in therapeutic response in an Indian population
Gene: GRK5
Variant/haplotype: rs2230345
Drug(s): Beta Blocking Agents
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AT + TT are associated with increased response to Beta Blocking Agents in people with Heart Failure as compared to genotype AA.
Notes: Heart failure patients taking beta blockers were evaluated for cardiac output and hospitalization-free survival.
Article: Effect of race and glucuronidation rates on the relationship between nicotine metabolite ratio and nicotine clearance
Gene: UGT2B10
Variant/haplotype: rs2942857
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of nicotine as compared to allele C.
Notes: No effect of the UGT2B10 variant genotypes on the ability of plasma nicotine metabolite ratio to predict nicotine clearance.
Article: Germline Polymorphisms as Biomarkers of Tumor Response in Colorectal Cancer Patients Treated with Anti-EGFR Monoclonal Antibodies: A Systematic Review and Meta-Analysis
Gene: PTGS2
Variant/haplotype: rs20417
Drug(s): cetuximab, panitumumab
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to cetuximab or panitumumab in people with Colorectal Neoplasms as compared to allele G.
Notes: Meta-analysis with 3 studies. The authors did not provide the exact number of patients but stated that "the median number of patients per analysis was 110 (range 50 - 740)". Most definitions of response were variations of the RECIST criteria.
Article: Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate
Gene: ITPA
Variant/haplotype: rs1127354
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C.
Article: Impact of NUDT15 polymorphisms on thiopurines-induced myelotoxicity and thiopurines tolerance dose
Gene: NUDT15
Variant/haplotype: rs116855232
Drug(s): azathioprine
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of azathioprine in people with Inflammatory Bowel Diseases and Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.
Notes: Meta-analysis with 13 studies. T allele carriers required 28% lower mean daily thiopurine dose as compared to those with the CC genotype. When patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD) were separated, there was a similar statistically significant dose reduction for both groups.
Article: Sulfasalazine disposition in a subject with 376C>T (nonsense mutation) and 421C>A variants in the ABCG2 gene
Gene: ABCG2
Variant/haplotype: rs72552713
Drug(s): sulfasalazine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype AG is associated with decreased metabolism of sulfasalazine in healthy individuals.
Notes: A single individual was compound heterozygous at rs72552713 (CT) and rs2231142 (GT) in BCRP as compared to other individuals who were heterozygous only at rs2231142 (GT). The individual  had a higher AUC(0,48 h) as compared to other other individuals who were only heterozygous at rs2231142 (GT) (779 vs.292 ± 97 µgml–1h, respectively) as well as a higher Cmax (50.3 vs.24.0±9.3 µgml–1, respectively), and a lower apparent oral clearance  (2.44 vs. 7.3 ±2.2 l h–1, respectively). Please note: alleles have been complemented to the + chromosomal strand.
Article: Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Gene: CYP3A7
Variant/haplotype: CYP3A7*1A, CYP3A7*1C
Drug(s): cortisone acetate
Phenotype category: Dosage
Significant: yes
Association: CYP3A7 *1C is associated with decreased dose of cortisone acetate in children with Adrenal Hyperplasia, Congenital as compared to CYP3A7 *1A.
Article: The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
Gene: NUDT15
Variant/haplotype: rs116855232
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CC + CT.
Notes: "Therapeutic dose of 6-mercaptopurine during maintenance therapy according to NUDT15 rs116855232 genotype in 92 pediatric acute lymphoblastic leukemia cases. The median 6MP dose intensity was 5%, 54.69% and 100% for the genotypes TT (n=1), CT (n=5) and CC (n=86), respectively (P=0.009)." Study also measured rs768324690, rs147390019, rs139551410, rs61973267 but these were monomorphic.
Article: CYP3A5 and ABCB1 genotype influence tacrolimus and sirolimus pharmacokinetics in renal transplant recipients
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): sirolimus, tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with metabolism of sirolimus or tacrolimus in people with Kidney Transplantation as compared to allele A.
Notes: No associations with tacrolimus or sirolimus pharmacokinetic parameters were seen for this SNP. Genotypes present were CC, CT, TT and A carriers. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study
Variant/haplotype: rs1611255
Drug(s): lithium
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to lithium in people with Bipolar Disorder as compared to allele C.
Notes: Please note that this SNP is given the ID rs144373461 in the paper.
Article: Association of corticotropin releasing hormone receptor 2 (CRHR2) genetic variants with acute bronchodilator response in asthma
Gene: CRHR2
Variant/haplotype: rs7793837
Drug(s): salbutamol, selective beta-2-adrenoreceptor agonists
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with decreased response to salbutamol and selective beta-2-adrenoreceptor agonists in people with Asthma as compared to allele A.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: AIDA
Variant/haplotype: rs3748631
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. Please note, alleles have been complemented to the + chromosomal strand.
Article: CYP3A4 and CYP3A5 Polymorphisms and Blood Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): amlodipine
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to amlodipine in people with Hypertension as compared to genotypes CC + CT.
Notes: No significant change in the likelihood of a patient reaching a target mean arterial pressure concentration of <= 92 mmHg or <= 107 mmHg was seen between genotypes. Please note alleles have been complemented to the plus chromosomal strand.
Article: Effect of UDP-Glucuronosyltransferase (UGT) 1A Polymorphism (rs8330 and rs10929303) on Glucuronidation Status of Acetaminophen
Gene: MROH2A, UGT1A, UGT1A1, UGT1A10, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9
Variant/haplotype: rs8330
Drug(s): acetaminophen glucuronide
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype GG is associated with increased formation of acetaminophen glucuronide in healthy individuals as compared to genotypes CC + CG.
Notes: Caution there is a possible strand issue with this C/G variant, authors describe variant as 2042C>G with C as major allele. Complemented here. Authors do not measure significance rather calculate the k value of concordance between genotype and speed of glucuronidation : homozygote reference = fast, heterozygote = intermediate and homozygote minor allele = slow.
Article: Impact of CYP3A4*22 on Pazopanib Pharmacokinetics in Cancer Patients
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): pazopanib
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes GT + TT is not associated with decreased clearance of pazopanib in people with Neoplasms as compared to genotype GG.
Notes: Alleles complemented to plus chromosomal strand.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: HTR2C
Variant/haplotype: rs3813929
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele C.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: CDH4
Variant/haplotype: rs4925300
Drug(s): ziprasidone
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with response to ziprasidone in people with Schizophrenia.
Notes: as measured by changes in PANSS-T (positive and negative syndrome scale total score), using a mixed model repeated measures approach. Examined 6789 SNPs - p-value of p< or equal to 5x10-4 was considered significant. It was unclear whether the allele was associated with an increased or decreased response to drug.
Article: Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway
Variant/haplotype: rs521093
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to antidepressants in people with Depressive Disorder, Major as compared to allele C.
Notes: Identity of minor allele not specified, so minor allele of dbSNP used here (T). Response considered to be successful with a 50% reduction at discharge of the Hamilton Rating Scale for Depression (HRSD17). Patients measured at admission and discharge, 4-6 weeks later. Specific antidepressants not listed.
Article: Polymorphisms and Clinical Outcome in Recurrent Ovarian Cancer Treated with Cyclophosphamide and Bevacizumab
Gene: CXCL8
Variant/haplotype: rs4073
Drug(s): bevacizumab, cyclophosphamide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AT are associated with decreased response to bevacizumab and cyclophosphamide in women with Ovarian Neoplasms as compared to genotype TT.
Article: A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers
Gene: MTHFR
Variant/haplotype: rs1801133
Drug(s): atorvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG are associated with decreased concentrations of atorvastatin in healthy individuals as compared to genotype GG.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): lopinavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with increased exposure to lopinavir in children with HIV Infections as compared to genotype TT.
Notes: Patients with the CT genotype had a significantly increased AUC0-12 of lopinavir compared to the TT genotype in patients treated with lopinavir/ritonavir. Variant referred to in the paper as T512C.
Article: NAMPT single-nucleotide polymorphism rs1319501 and visfatin/NAMPT affect nitric oxide formation, sFlt-1 and antihypertensive therapy response in preeclampsia
Gene: NAMPT
Variant/haplotype: rs1319501
Drug(s): nitric oxide
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased concentrations of nitric oxide in women with Pre-Eclampsia as compared to genotypes CC + CT.
Notes: Authors state "The TT genotype for the NAMPT SNP rs1319501 (T>C) was associated with higher nitrite concentrations in pregnant with PE nonresponsive to antihypertensive therapy."" We found no significant effects of genotypes for the NAMPT SNPs on nitrite concentrations in HP or PE patients."
Article: The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response
Gene: AQP2
Variant/haplotype: rs7314734
Drug(s): platinum
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to platinum in people with Lung Neoplasms as compared to allele 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: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients
Gene: MTHFR
Variant/haplotype: rs1801133
Drug(s): fluorouracil, leucovorin, oxaliplatin
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased response to fluorouracil, leucovorin and oxaliplatin in people with Colorectal Neoplasms as compared to allele G.
Article: β2-Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies
Gene: ADRB2
Variant/haplotype: rs1042714
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to atenolol or metoprolol in people with Tachycardia as compared to genotypes CG + GG.
Notes: Patients with the CC genotype had a significantly greater decrease in heart rate than patients with the CG or GG genotypes. Note that this association was only significant in white patients.
Article: Effects of genetic variation in H3K79 methylation regulatory genes on clinical blood pressure and blood pressure response to hydrochlorothiazide
Gene: DOT1L
Variant/haplotype: rs2269879
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT are associated with increased response to hydrochlorothiazide in people with Hypertension as compared to genotype CC.
Notes: In the PEAR cohort, in Whites: 5.5 mmHg greater mean systolic bp response(p = 0.0002 uncorrected) and a 3.5 mmHg greater mean diastolic bp response (p = 0.0016 uncorrected). [stat_test:linear regression].  More than 90% of participants were receiving 25 mg/day HCTZ (the rest received 12.5 mg/day).  This did not replicate significantly in a second cohort(GERA) and authors concluded that there could possibly be an association between this SNP and  blood pressure response to HCTZ in Caucasians, but that it requires further investigation.  Significance for this segment of the study was set at p < 0.01 for a partially corrected p, and in Whites, this level was met when a partial correction for multiple testing was done.  But for a compound, corrected p predetermined by the authors to be the significance point for both segments of the study, the significance test  failed.
Article: Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *2 is associated with increased resistance to clopidogrel in people with Coronary Disease as compared to CYP2C19 *1.
Notes: *2 was significant in Co-dominat, Dominant, and Recessive models.