shlokn/autogkb huggingface dataset:
Article: Influence of ABCC2 and ABCC4 Polymorphisms on Tenofovir Plasma Concentrations in Thai HIV-Infected Patients
Gene: ABCC4
Variant/haplotype: rs3742106
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AC + CC is associated with increased concentrations of tenofovir in people with HIV Infections as compared to genotype AA.
Notes: Patients with ABCC4 4131 TG or GG genotype had a 30% increase of mean tenofovir plasma concentration.
Article: Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes
Gene: SLCO1B1
Variant/haplotype: rs4149015
Drug(s): pravastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with increased response to pravastatin in children with Hyperlipoproteinemia Type II as compared to genotype GG.
Notes: 2 patients with the AG genotype (who also had rs4149056 genotype TC) had significantly higher increases in HDL-cholesterol after treatment. Genotypes were not associated with lipid-lowering effect. This variant was described as -11187G>A.
Article: GRIK4 polymorphism and its association with antidepressant response in depressed patients: a meta-analysis
Gene: GRIK4
Variant/haplotype: rs1954787
Drug(s): antidepressants
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to antidepressants in people with Depressive Disorder, Major as compared to genotype TT.
Notes: Meta-analysis combining 5 studies.
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Variant/haplotype: rs3761372
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with increased 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: 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: rs2236256
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methadone in people with Heroin Dependence as compared to allele A.
Notes: This SNP was not significantly associated with compliance with methadone maintenance therapy or 'negative rate of morphine urine test'.
Article: Genotypic and Phenotypic Factors Influencing Drug Response in Mexican Patients With Type 2 Diabetes Mellitus
Gene: ABCC8
Variant/haplotype: rs757110
Drug(s): sulfonamides, urea derivatives
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + CC is associated with increased response to sulfonamides, urea derivatives in people with Diabetes Mellitus as compared to genotype AC.
Notes: The AC genotype was associated with increased response to sulfonylureas (a greater than or equal to 7% decrease in Hb1Ac levels at least 3 months after beginning treatment).
Article: CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2B6 *6 is associated with increased concentrations of efavirenz in people with HIV as compared to CYP2B6 *1/*1.
Article: The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients
Gene: SLC22A1
Variant/haplotype: rs594709
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to genotype GG.
Notes: Looked at changes in the following as measures of metformin response between AA/GA (n=50) and GG genotype (n=3): fasting blood glucose (p=0.112), postprandial blood glucose (p=0.171), fasting insulting (p=0.015), postprandial insulin (p=0.259), glycosylated hemoglobin (p=0.227), triglycerides (p=p=0.434), total cholesterol (p=0.224), low-density lipoprotein (p=0.451), high-density lipoprotein (p=0.399), homeostasis model assessment of insulin resistance (p=0.081), homeostasis model assessment of insulin sensitivity (p=0.001), homeostasis model assessment of B cell function (p=0.493), and quantitative insulin sensitivity check index (p=0.002). Also, found an interaction between this SNP and SLC47A1 rs2289669, with patients with rs594709 AA genotypes and rs2289669 AA genotypes showing higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p-0.014) than patients with rs2289669 GA or GG genotypes. Patients with rs594709 G allele carriers and also rs2289669 AA genotype showed greater decrease in TChol (p=0.013) than GA or GG genotypes.
Article: CYP3A5 Gene Variation Influences Cyclosporine A Metabolite Formation and Renal Cyclosporine Disposition
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): cyclosporine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CC + CT are associated with increased metabolism of cyclosporine in healthy individuals as compared to genotype TT.
Notes: Increased metabolism was shown by increased area under the concentration-time curve (AUC) from time 0 to infinity (AUC0-infinity, units = ng hr/mL) and increased AUCmetabolite/AUCcyclosporine for the metabolites AM19 and AM1c9. These metabolites are secondary metabolites of cyclosporine, formed through the conversion of the cyclosporine primary metabolites AM1 and AM1c, respectively, by CYP3A5. Increased metabolism was also shown by decreased urinary clearance (CL, units = mL/min) and decreased estimated glomeruler filtration rate-normalized apparent urinary clearance (CL / eGFR) of cyclosporine.
Article: Sub‐ and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study
Gene: CYP2B6
Variant/haplotype: rs35303484
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AG is associated with increased concentrations of efavirenz in children with HIV infectious disease as compared to genotype AA.
Notes: "heterozygosity in CYP2B6 c.136A>G predicted higher loge EFV plasma concentration. The latter SNP occurred in only one participant (id. 79), who despite being predicted as an IM (composite genotype 516GG|983TC), maintained very high EFV plasma levels (across study median of 12 539 ng mL−1, range 11 163–23 715 ng mL−1). "
Article: Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study
Gene: ACE
Variant/haplotype: rs1799752
Drug(s): captopril
Phenotype category: Efficacy
Significant: yes
Association: Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to captopril in men with Pulmonary Disease, Chronic Obstructive as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.
Notes: The ATA.../ATA... genotype is associated with increased mixed venous oxygen tension (PvO2; units = mmHg) and decreased lactate concentration (units = mmol/l) after exercise, as compared to patients with the remaining genotypes. This indicates an increased response to captopril.
Article: Association of Regulatory Genetic Variants for Protein Kinase C α with Mortality and Drug Efficacy in Patients with Heart Failure
Gene: PRKCA
Variant/haplotype: rs9909004
Drug(s): "Ace Inhibitors, Plain", "Angiotensin II Antagonists", "Beta Blocking Agents"
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to Ace Inhibitors, Plain, Angiotensin II Antagonists or Beta Blocking Agents in people with Heart Failure as compared to allele T.
Notes: The authors note that this variant was in strong LD with rs9303504.
Article: A Single Nucleotide Polymorphism in cBIM Is Associated with a Slower Achievement of Major Molecular Response in Chronic Myeloid Leukaemia Treated with Imatinib
Gene: BCL2L11
Variant/haplotype: rs724710
Drug(s): imatinib
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to allele C.
Notes: The T allele was also significantly associated with presence of mutations in the kinase domain of the BCR-ABL fusion protein and resistance to tyrosine kinase inhibitors. Response was defined as a ratio of BCR-ABl/ABl of less than or equal to 0.1% by 18 months of treatment with imatinib.
Article: HLA-G 3’UTR Polymorphisms Impact the Prognosis of Stage II-III CRC Patients in Fluoropyrimidine-Based Treatment
Gene: HLA-G
Variant/haplotype: rs17179101
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: no
Association: Genotype AC is not associated with response to capecitabine or fluorouracil in people with Colorectal Neoplasms as compared to genotype CC.
Notes: The authors examined disease free survival (DFS) as well as overall survival (OS). Neither were significantly associated with any genotype.
Article: A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression
Gene: HTR7
Variant/haplotype: rs7905446
Drug(s): atomoxetine, desvenlafaxine, duloxetine, Selective serotonin reuptake inhibitors, venlafaxine
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with decreased response to atomoxetine, desvenlafaxine, duloxetine, Selective serotonin reuptake inhibitors or venlafaxine in people with Depression as compared to genotypes GG + GT.
Notes: The TT genotype was associated with non-remission, white the GG and GT genotypes were associated with treatment remission at 6 weeks.; This association was seen with SSRI and SNRI treatment however, the exact drugs used in treatment were not specified.
Article: Pharmacokinetics and pharmacogenetics of the MEK1/2 inhibitor, selumetinib, in Asian and Western healthy subjects: a pooled analysis
Gene: CYP2C19
Variant/haplotype: rs12248560
Drug(s): selumetinib
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with dose of selumetinib in healthy individuals as compared to allele C.
Notes: Not associated with normalized dose when allele was assessed within ethnic groups (Asian, White, Black) and when all ethnic groups were pooled together.
Article: Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Genotypes AA + AG are associated with increased response to risperidone in people with Schizophrenia as compared to genotype GG.
Notes: Alleles given as reverse strand C and T. Efficacy measured with reduction in PANSS total score reduced rate.
Article: Gene‐Wide Tagging Study of the Association Between KCNT1 Polymorphisms and the Susceptibility and Efficacy of Genetic Generalized Epilepsy in Chinese Population
Gene: KCNT1
Variant/haplotype: rs10118746
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to antiepileptics in people with Epilepsy, Generalized as compared to allele G.
Notes: No significant differences in genotype frequencies were seen between patients who were responsive to antiepileptic drugs (n=279; those who had not experienced any type of seizure for a minimum of 1 year after receiving antiepileptic drugs) and patients who were resistant to antiepileptic drugs (n=204; those who had at least four seizures during the previous year while trying at least three antiepileptic medications at the maximal tolerated doses).
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: GABRE
Variant/haplotype: rs1139916
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 C.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs9479757
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 G.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: Laboratory and Clinical Outcomes of Pharmacogenetic vs. Clinical Protocols for Warfarin Initiation in Orthopedic Patients
Gene: CYP2C9
Variant/haplotype: CYP2C9*2, CYP2C9*3
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: CYP2C9 *2 + *3 are associated with dose of warfarin.
Notes: Generation of an algorithm to predict warfarin dose based on these variants as well as VKORC1 rs9923231 and clinical factors, as well as analyses on the performance of the algorithm vs a clinical algorithm.
Article: Possible association of norepinephrine transporter -3081(A/T) polymorphism with methylphenidate response in attention deficit hyperactivity disorder
Gene: SLC6A2
Variant/haplotype: rs5569
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to methylphenidate in children with Attention Deficit Disorder with Hyperactivity as compared to genotypes AA + AG.
Notes: ADHD Rating Scale-IV (ARS) and Clinical Global Impression (CGI) were used to assess response.
Article: Impact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European‐Americans and Egyptians
Gene: GGCX
Variant/haplotype: rs12714145
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Genotype CC is not associated with dose of warfarin as compared to genotypes CT + TT.
Notes: in European-Americans, and Egyptians.
Article: LGR5 rs17109924 is a predictive genetic biomarker for time to recurrence in patients with colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy
Gene: LGR5
Variant/haplotype: rs17109924
Drug(s): fluorouracil
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to fluorouracil in people with Colonic Neoplasms as compared to genotype TT.
Notes: Patients who received 5-fluorouracil-based adjuvant chemotherapy and underwent surgery, who carried at least one C allele, had significantly increased time to tumor recurrence as compared to those with the TT genotype. No association was seen for patients who only underwent surgery (p=0.728; n=208).
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: rs2302663
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to fentanyl in people with Pain, Postoperative as compared to allele G.
Article: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): carbamazepine
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Allele A is not associated with increased dose of carbamazepine in people with Epilepsy as compared to allele G.
Article: Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): gefitinib
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with increased response to gefitinib in people with Carcinoma, Non-Small-Cell Lung as compared to genotypes GT + TT.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: STK11
Variant/haplotype: rs2301759
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele T.
Notes: Authors looked at candidate genes in patients that had previously had genome sequencing. They look quite far outside of conventional gene boundaries. "For each candidate gene we selected SNPs 50 kb upstream and downstream of each gene using 1000 genomes project variants and NCBI build 37 as the reference genome." Table 2 shows rs2301759 as top SNP for STK11
Article: Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis
Gene: CYP2D6
Variant/haplotype: CYP2D6 ultrarapid metabolizer
Drug(s): paroxetine
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 ultrarapid metabolizer is associated with decreased clinical benefit to paroxetine in people with Depressive Disorder, Major as compared to CYP2D6 normal metabolizer.
Notes: "At the 4-week treatment endpoint (Supplementary Table S2), we observed a trend of lower percentage improvement in symptom severity for UMs compared to EMs in the MDD group, after adjusting for predefined demographic covariates (age and sex), which was not statistically significant (multiple linear regression, standardized β = −0.93, SE = 0.50, P = 0.07). However, in post-hoc analysis, when further adjusting for current episode duration, baseline symptom severity, daily dose, and adjunctive medication status, the effect of UM became marginally statistically significant (standardized β = −0.98, SE = 0.50, P = 0.049)."
Article: CYP2C9*1B Promoter Polymorphisms, in Linkage with CYP2C19*2, Affect Phenytoin Autoinduction of Clearance and Maintenance Dose
Gene: CYP2C9
Variant/haplotype: rs71486745
Drug(s): phenytoin
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotypes GT/del + del/del are associated with decreased dose of phenytoin in people with Epilepsy as compared to genotype GTGT.
Notes: Statistics given for haplotype *1B measured by rs71486745delTG and rs12782374G>A.
Article: Genetic Polymorphism at Val80 (rs700518) of the CYP19A1 Gene is Associated with Body Composition Changes in Women on Aromatase Inhibitors for ER (+) Breast Cancer
Gene: CYP19A1
Variant/haplotype: rs700518
Drug(s): Enzyme inhibitors
Phenotype category: Other
Significant: yes
Association: Genotype CC is associated with response to Enzyme inhibitors in women with Breast Neoplasms as compared to genotypes CC + CT.
Notes: Please note the article studied changes in body composition. CC carriers developed a significant increase in truncal fat mass index (P=0.03) and a significant decrease in fat-free mass index (P=0.01) at 12 months compared to CT/TT carriers.
Article: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients
Gene: MTHFR
Variant/haplotype: rs1801131
Drug(s): fluorouracil, leucovorin, oxaliplatin
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to fluorouracil, leucovorin and oxaliplatin in people with Colorectal Neoplasms as compared to allele T.
Article: Laboratory and Clinical Outcomes of Pharmacogenetic vs. Clinical Protocols for Warfarin Initiation in Orthopedic Patients
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele A is associated with dose of warfarin as compared to allele G.
Notes: Generation of an algorithm to predict warfarin dose based on this rsID as well as CYP2C9*2 and *3 and clinical factors, as well as analyses on the performance of the algorithm vs a clinical algorithm.
Article: Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*5
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*5 is associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: In this meta-analysis of warfarin Dose in Black-African Patients, CYP2C9*5 allele is associated with 13.4mg/week less warfarin dose requirement compared to wild-type homozygotes.
Article: Influence of novel CYP2C‐haplotype on proton pump inhibitor pharmacokinetics in children
Gene: CYP2C18
Variant/haplotype: rs2860840
Drug(s): lansoprazole, pantoprazole
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with increased metabolism of lansoprazole or pantoprazole in children as compared to allele C.
Notes: "This detailed PK analysis of 45 children who received one or more of the three study PPIs (oral pantoprazole, IV pantoprazole, oral lansoprazole) at different study visits found the CYP2C:TG haplotype to have no measurable impact on CYP2C19‐mediated metabolism of PPIs in vivo" The unofficial haplotype CYP2C:TG comprises rs2860840T and rs11188059G.
Article: Comprehensive characterization of pharmacogenetic variants in TPMT and NUDT15 in children with acute lymphoblastic leukemia
Gene: NUDT15
Variant/haplotype: rs73189762
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
Notes: This was only significant in the discovery cohort and not the validation cohort. The discovery cohort had one TT homozygote, the validation had zero (supplemental figures). Note, the variant is approximately 50kb downstream of the coding region of NUDT15.
Article: GENOMIC ASSOCIATION ANALYSIS IDENTIFIES MULTIPLE LOCI INFLUENCING ANTIHYPERTENSIVE RESPONSE TO AN ANGIOTENSIN II RECEPTOR BLOCKER
Gene: GPR83
Variant/haplotype: rs3758785
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to hydrochlorothiazide in people with essential hypertension as compared to genotype AA.
Notes: Heterozygotes had intermediate response and pattern was the same for both SBP and DBP.
Article: The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study
Gene: ADRA2A
Variant/haplotype: rs2484516
Drug(s): dexmedetomidine
Phenotype category: Dosage
Significant: no
Association: Genotype CC is not associated with dose of dexmedetomidine in men as compared to genotype CG.
Article: Relevance of CYP2B6 and CYP2D6 genotypes to methadone pharmacokinetics and response in the OPAL study
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): (S)-methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes GT + TT are associated with increased concentrations of (S)-methadone in people with Opioid-Related Disorders as compared to genotype GG.
Notes: Significance was lost following multivariate analysis.