shlokn/autogkb huggingface dataset:
Article: Impact of IL6R genetic variants on treatment efficacy and toxicity response to sarilumab in rheumatoid arthritis
Gene: IL6R
Variant/haplotype: rs11265618
Drug(s): sarilumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to sarilumab in people with Arthritis, Rheumatoid as compared to genotypes CT + TT.
Notes: "For rs4329505 and rs11265618, the genetic model that best fit the data was the dominant model, as patients homozygous for the wild-type allele (TT for rs4329505 and CC for rs11265618) showed better remission rates than the other patients; specifically, remission rates (CDAI-LDA) were 73.5% vs. 44.4% (p = 0.039) and the quantitative improvement in DAS28 was 2.9 vs. 2.0 (p = 0.048). No significant differences were found for DAS28 LDA, CDAI improvement, and/or EULAR response rates." "A linked inheritance was observed between rs4329505 and rs11265618, as all individuals carrying the T allele for rs4329505 also had the C allele for rs11265618, and vice versa. "
Article: Genetic Analysis of Mu and Kappa Opioid Receptor and COMT Enzyme in Cancer Pain Tunisian Patients Under Opioid Treatment
Gene: OPRM1
Variant/haplotype: rs17174629
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: no
Association: Allele G is not associated with dose of morphine in people with Pain as compared to allele A.
Notes: No association was observed between this variant and a patient's initial dose requirement or their need to escalate their dose of morphine.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: PURA
Variant/haplotype: rs2013169
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to methylphenidate in people with Attention Deficit Disorder with Hyperactivity.
Notes: The authors carried out a GWAS in a Spanish cohort of pediatric patients, than performed a meta-analysis using data from the Spanish cohort and data from a Brazilian adult patient cohort.; This variant was not significant in the meta-analysis after Bonferroni correction had been applied, and was nominally significant (i.e did not reach genome-wide significance) in the initial GWAS in the Spanish cohort.; Response was measured on the Clinical Global Impression-Improvement scale (CGI-I). A CGI-I score of two points or less after eight weeks of treatment was considered a good response.
Article: Meta-Analysis of the SLCO1B1 c.521T>C Variant Reveals Slight Influence on the Lipid-Lowering Efficacy of Statins
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): hmg coa reductase inhibitors
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CT are not associated with decreased response to hmg coa reductase inhibitors as compared to genotype TT.
Notes: Meta analysis did not significant association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism. However, the wild genotype improved the lipid-lowering efficacy of simvastatin.
Article: Pharmacogenomic Next-Generation DNA Sequencing: Lessons from the Identification and Functional Characterization of Variants of Unknown Significance in CYP2C9 and CYP2C19
Gene: CYP2C19
Variant/haplotype: rs1187513719
Drug(s): mephenytoin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is associated with decreased clearance of mephenytoin as compared to allele A.
Notes: In vitro analysis showed that intrinsic clearance of S-mephenytoin by CYP2C19 protein containing the A allele was 57.9% of that of the WT protein. However, this difference was not found to be statistically significant. Variant referred to as 578A>G in the paper.
Article: Genotype-guided tacrolimus dosing in African American kidney transplant recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*3, CYP3A5*6, CYP3A5*7
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP3A5 *3 + *6 + *7 are associated with decreased clearance of tacrolimus in people with Kidney Transplantation.
Notes: This study generated an algorithm for predicting tacrolimus daily dose based on tacrolimus typical value of clearance (TVCl/F) that included CYP3A5 alleles *3, *6 and *7. It also found that in subjects with the *1/*3, *1/*6 and *1/*7 genotypes had TVCl/F decreased by 16.2%, 8.2% and 24.1% respectively, and subjects with the *3/*3, *3/*6, *3/*7 or *6/*7 had it decreased by 51%, 36.5%, 54.5% and 44.2% respectively, as compared to the *1/*1 genotype.
Article: The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): warfarin
Phenotype category: Other, Metabolism/PK
Significant: not stated
Association: Genotype CT is associated with increased clearance of warfarin as compared to genotype CC.
Notes: For R-Warfarin in a model that included bodyweight, age and CYP2C19 rs3814637.
Article: SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer
Gene: SLC19A1
Variant/haplotype: rs1051266
Drug(s): capecitabine, fluorouracil, irinotecan, leucovorin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to capecitabine, fluorouracil, irinotecan or leucovorin in people with Colorectal Neoplasms as compared to genotypes CT + TT.
Notes: This SNP was presented as an A>G nucleotide change. Patients were split into two groups based on treatment. One group received irinotecan, fluorouracil, and leucovorin, and the other group received irinotecan and capecitabine. Patients with the GG genotype showed significantly greater rapid response rate as compared to patients carrying the A allele. In addition, when combined with rs2306283, patients homozygous for the G allele for this SNP and carrying the A allele at rs2306283 had significantly higher rapid response rates than patients with any other combination of genotypes.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Variant/haplotype: rs1995152
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with trough concentration of vancomycin as compared to allele A.
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 of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers
Gene: CYP2A6
Variant/haplotype: CYP2A6*1, CYP2A6*2, CYP2A6*4, CYP2A6*9, CYP2A6*12, CYP2A6*17, CYP2A6*20, CYP2A6*23, CYP2A6*24, CYP2A6*25, CYP2A6*26, CYP2A6*27, CYP2A6*28, CYP2A6*35
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*2 + *1/*4 + *1/*17 + *1/*20 + *1/*23 + *1/*24 + *1/*25 + *1/*26 + *1/*27 + *1/*28 + *1/*35 + *9/*9 + *17/*17 + *20/*20 + *35/*35 are associated with decreased metabolism of nicotine as compared to CYP2A6 *1/*9 + *1/*12.
Article: Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry
Gene: F2
Variant/haplotype: rs5896
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Genotype TT is associated with decreased dose of warfarin as compared to genotypes CC + CT.
Notes: in a Southern Brazilian population of European ancestry. This F2 variant is not associated independently with warfarin dose. However, when it was included in the multiple linear regression (after controlling for covariates), statistically significant results were obtained.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): (S)-methadone
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2B6 *6/*6 is associated with increased concentrations of (S)-methadone in people with Opioid-Related Disorders as compared to CYP2B6 *1/*1.
Notes: No details about which specific variants/alleles were tested for, however the authors state that genotyping of *1/*6 individuals did not exclude the possibility of them actually being *4/*9.
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Gene: FCGR3A
Variant/haplotype: rs396991
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with clearance of tenofovir in people with HIV Infections as compared to allele A.
Notes: Significance threshold was set at 4.5E-3.
Article: Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria
Gene: C3
Variant/haplotype: rs2230199
Drug(s): eculizumab
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CG is not associated with response to eculizumab in people with paroxysmal nocturnal hemoglobinuria as compared to genotype GG.
Notes: Response was defined as no red blood cell transfusion at any time after the first 6 months on eculizumab treatment (patients had a median follow-up of 52 months, range of 11-98 months). In the paper, GG = Slow/Slow.
Article: Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol
Gene: ABCC2
Variant/haplotype: rs2273697
Drug(s): cisplatin, doxorubicin, methotrexate
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AG is associated with decreased clinical benefit to cisplatin, doxorubicin and methotrexate in people with Osteosarcoma as compared to genotype GG.
Notes: "For ABCC2 rs2273697, 50% of patients with the GG genotype presented poor pathological response, compared to 81.8% of patients with GA or AA genotypes (p = 0.02 in a dominant model)." "Multivariate analyses including these two SNPs and age, gender and tumor site as covariates showed significant associations for both genetic variants: ABCC2 rs2273697 (OR 12.3, 95% CI 2.3–66.2; p = 0.003) and ERCC2 rs1799793 (OR 9.6, 95% CI 2.1–43.2; p = 0.003). However, these associations were not statistically significant after the Bonferroni test." "Pathological response classification was dichotomized into good response (tumor necrosis ≥ 90%) and poor response (tumor necrosis (<90%). "
Article: ABC Transporter Polymorphisms are Associated with Irinotecan Pharmacokinetics and Neutropenia
Gene: ABCC1
Variant/haplotype: rs212082
Drug(s): SN-38
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes AG + GG are not associated with 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: CYP3A4 and CYP3A5 Polymorphisms and Blood Pressure Response to Amlodipine among African-American Men and Women with Early Hypertensive Renal Disease
Gene: CYP3A4
Variant/haplotype: rs2246709
Drug(s): amlodipine
Phenotype category: Efficacy
Significant: no
Association: Genotypes AG + GG are not associated with response to amlodipine in men with Hypertension as compared to genotype AA.
Notes: No significant change in the likelihood of a man 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 ADRA2A gene polymorphisms on the anesthetic and analgesic effects of dexmedetomidine in Chinese Han women with cesarean section
Gene: ADRA2A
Variant/haplotype: rs1800035
Drug(s): dexmedetomidine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CG + GG are associated with decreased response to dexmedetomidine in women with Pain, Postoperative as compared to genotype CC.
Notes: Patients with the CC genotype had significantly increased pain thresholds and significantly reduced VAS pain scores post-surgery than women with the CG or GG genotypes. There was no significant difference in pain thresholds between genotype group pre-surgery.
Article: Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects
Gene: ADGRL3
Variant/haplotype: rs6858066
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to allele A.
Notes: Clinical Global Impression-Severity (CGI-S) scale and the Children’s Global Assessment Scale (CGAS).
Article: Host Genetic Factors and Dendritic Cell Responses Associated with the Outcome of Interferon/Ribavirin Treatment in HIV-1/HCV Co-Infected Individuals
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: not stated
Association: Genotype CC is associated with increased response to peginterferon alfa-2b and ribavirin in people with Hepatitis C and HIV Infections as compared to genotype TT.
Notes: rs12979860 seems to be a better predictor of treatment outcome than rs4803217 and ss469415590 in HCV/HIV co-infective patients."rs12979860 showed a strong association with treatment response with ~60% of individuals with the most favorable genotype CC and only 25% of individuals with the least favorable genotype TT achieving sustained virological response (SVR)." "Approximately 33% of the individuals with rs4803217 intermediate genotype GT and only 25% of the individuals with least favorable genotype TT cleared the virus.; Approximately 33% of the individuals with most favorable ss469415590 genotype TT/TT and only 25% of the individuals with least favorable genotype delG/delG cleared the virus"
Article: Targeted pharmacogenetic analysis of antipsychotic response in the CATIE study
Gene: NPAS3
Variant/haplotype: rs1315115
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with response to risperidone 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.  Please note: the allele was reported as C (though this gene is found on the plus chromosomal strand). It was unclear whether the allele was associated with an increased or decreased response to drug.
Article: Safety of Voriconazole in a Patient with CYP2C9*2/CYP2C9*2 Genotype
Gene: CYP2C9
Variant/haplotype: CYP2C9*2
Drug(s): voriconazole
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C9 *2/*2 is not associated with concentrations of voriconazole.
Notes: Case report. One Caucasian patient homozygous for the CYP2C9 *2 allele (i.e. a poor metabolizer) and homozygous for the CYP2C19 wild-type *1 allele. The apparent oral clearance, area under the concentration-time curve from zero hours to infinity (AUC0-inf), volume of distribution and half-life time were "not different" (though note that they were not identical) between the patient with the *2/*2 genotype and healthy volunteers from a previous study with the *1/*1 genotype. No statistical analyses were done.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: SCN9A
Variant/haplotype: rs6746030
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele G.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Impact of SLCO1B3 Polymorphisms on Clinical Outcomes in Lung Allograft Recipients Receiving Mycophenolic Acid
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): azathioprine, mycophenolic acid
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to azathioprine or mycophenolic acid in people with lung transplantation as compared to allele A.
Notes: No significant association between this variant and survival post-transplantation or development of acute cellular rejection, lymphocytic bronchiolitis or chronic lung allograft dysfunction (CLAD).
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs1042114
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to buprenorphine in people with Opioid-Related Disorders as compared to allele T.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.
Article: Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): sunitinib
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AG + GG.
Notes: The genotype was associated with decreased clinical benefit but it was not associated with progression free survival, or overall survival, Clinical benefit was defined as either partial response or stable disease. This was more significant when calculated for the haplotype rs1045642 T, rs1128503 T, and rs2032582 T. Please note, alleles have been complemented to the + chromosomal strand.
Article: Association of the PPP3CA c.249G>A variant with clinical outcomes of tacrolimus-based therapy in kidney transplant recipients
Gene: PPP3CA
Variant/haplotype: rs3730251
Drug(s): tacrolimus
Phenotype category: Efficacy, Toxicity
Significant: no
Association: Genotypes CT + TT are not associated with response to tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: This variant did not influence clinical outcomes of patients receiving tacrolimus, including eGFR, levels of urea, creatinine, glucose, lipids, or blood counts, biopsy-confirmed acute rejection, delayed graft function, renal function, or adverse events. The authors note that those with the CT or TT genotype did have a 3.05-fold increased probability of treatment-induced blood and lymphatic system disorders as compared to the CC genotype, but this result was not maintained after adjusting for body weight and CYP3A5*3 status. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement
Gene: EPHX1
Variant/haplotype: rs2260863
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype CG is associated with increased dose of warfarin in people with heart valve replacement as compared to genotype CC.
Article: No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA
Gene: SLC6A2
Variant/haplotype: rs2242446
Drug(s): 3,4-methylenedioxymethamphetamine
Phenotype category: Other
Significant: yes
Association: Genotype TT are associated with decreased response to 3,4-methylenedioxymethamphetamine as compared to genotypes CC + CT.
Notes: The TT genotype was associated with decreased heart rate, but not plasma concentrations , or mean arterial pressure.
Article: Impact of STAT6 Variants on the Response to Proton Pump Inhibitors and Comorbidities in Patients with Eosinophilic Esophagitis
Gene: STAT6
Variant/haplotype: rs12368672
Drug(s): Proton pump inhibitors
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CG is associated with increased response to Proton pump inhibitors in people with eosinophilic esophagitis as compared to genotype GG.
Notes: as measured by PEC Reduction and EREFS Score Reduction. Alleles complemented. "Patients with the STAT6 rs12368672 C/C genotype showed a lower reduction in EREFS score compared to patients with G/C + G/G genotypes (p = 0.011) (Table 5). Furthermore, a higher EREFS score reduction was observed in individuals with ABCB1 rs2032582 T/T+T/G genotypes compared to those with A/A+G/A+G/G genotypes (p = 0.045) (Table 5); none of these differences reached the threshold for statistical significance after the Bonferroni correction for multiple comparisons "
Article: G Protein-Coupled Receptor Kinase 5 Gene Polymorphisms Are Associated with Postoperative Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery in Patients Receiving Beta-Blockers
Gene: GRK5
Variant/haplotype: rs3740563
Drug(s): Beta Blocking Agents
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to Beta Blocking Agents in people with Coronary Artery Disease as compared to allele C.
Notes: Single-nucleotide polymorphisms in 10 candidate genes were tested for association with atrial fibrillation after coronary artery bypass grafting despite perioperative beta blocker therapy. rs3740563 is in strong linkage disequilibrium with rs4752292.
Article: Escitalopram and sertraline population pharmacokinetic analysis in pediatric patients
Gene: CYP2C19
Variant/haplotype: CYP2C19 poor metabolizer
Drug(s): sertraline
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 intermediate metabolizer and poor metabolizer is associated with decreased clearance of sertraline in children as compared to CYP2C19 normal metabolizer and ultrarapid metabolizer and rapid metabolizer.
Notes: "No diference in CL/F between; patients who are normal, rapid, and ultrarapid metabolizers; was detected, and so these phenotypes were grouped during model development" "We observed; that poor and intermediate metabolizers had on average 65%; and 34% slower CL/F compared to normal, rapid, and ultrarapid metabolizers"
Article: Population Pharmacokinetic and Pharmacogenetic Analysis of Nevirapine in Hypersensitive and Tolerant HIV-Infected Patients from Malawi
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): nevirapine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT is associated with decreased clearance of nevirapine in people with HIV Infections as compared to genotype GG.
Notes: Those with the GT and TT genotypes had a 7.6% and a 19.5% reduction in clearance of nevirapine, respectively, as compared to those with the GG genotype. This SNP remained in the multiple SNP analysis model after backwards elimination.
Article: Single Dose, CYP2D6 Genotype-Stratified Pharmacokinetic Study of Atomoxetine in Children with ADHD
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*4xN, CYP2D6*5, CYP2D6*9, CYP2D6*10, CYP2D6*29, CYP2D6*41
Drug(s): atomoxetine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *4/*4xN + *4/*4 are associated with decreased clearance of atomoxetine in children with Attention Deficit Disorder with Hyperactivity as compared to CYP2D6 *1/*1 + *1/ *2 + *2/*4 + *1/*4 + *1/*3 + *2/*5 + *10/*41 + *9/*29.
Notes: single dose study with an average of 0.43 mg/kg. Children received either 10, 18, 25, 30 or 40 mg atomoxetine.
Article: The role of organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics
Gene: SLCO1B3
Variant/haplotype: rs7311358
Drug(s): mycophenolate mofetil
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with clearance of mycophenolate mofetil in people with Kidney Transplantation as compared to allele G.
Notes: This finding is for patients also treated with cyclosporine.