shlokn/autogkb huggingface dataset:
Article: Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy
Gene: CYP19A1
Variant/haplotype: rs749292
Drug(s): triglycerides
Phenotype category: Other
Significant: yes
Association: Allele A is associated with decreased concentrations of triglycerides in women with Breast Neoplasms and Menopause as compared to allele G.
Notes: when taking letrozole. Data are from a sub-analysis of the Exemestane and Letrozole Pharmacogenomics (ELPh) study, where post-menopausal women with early stage breast cancer were randomized to receive exemestane or letrozole. Of the 303 eligible women, 160 were randomized to the letrozole group, 52 of whom were also taking LLA. This SNP was associated with decreases in triglycerides ranging from 39.3-20.2 mg/dL using a recessive and additive model, respectively.
Article: Predictors of clozapine concentration and psychiatric symptoms in patients with schizophrenia
Gene: ABCB1
Variant/haplotype: rs7787082
Drug(s): clozapine
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased clinical benefit to clozapine in people with Schizophrenia or Psychotic Disorder as compared to allele G.
Notes: Alleles complemented. Table does not state which allele or direction of effect for these SNPs, so assuming minor allele and benefit, PANSS beta is in Table negative. "four SNPs in two genes were significantly associated with the total PANSS score: rs7787082 and rs10248420 in ABCB1 and rs2133251840 and rs762502 in DRD4 (Table 5). Among these, only one SNP in DRD4 (rs2133251840) resulted in different total PANSS scores at visits 3 and 4 according to its genotype"
Article: Effects of Opioid Receptor Gene Variation on Targeted Nalmefene Treatment in Heavy Drinkers
Gene: OPRD1
Variant/haplotype: rs2234918
Drug(s): nalmefene
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to nalmefene in people with Alcoholism as compared to allele T.
Article: Genetic and environmental factors determining clinical outcomes and cost of warfarin therapy: a prospective study
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin as compared to allele C.
Article: Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population
Gene: CHRNA3
Variant/haplotype: rs2869546
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele C is not associated with exposure to nicotine in men as compared to allele T.
Notes: No significant association between this allele and status as a smoker or non-smoker.
Article: Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE
Gene: CYP2C8
Variant/haplotype: rs7910936
Drug(s): desethylchloroquine, hydroxychloroquine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with increased concentrations of desethylchloroquine or hydroxychloroquine in people with Lupus Erythematosus, Systemic as compared to allele T.
Notes: "The C allele of CYP2C8 (rs7910936) was related to higher HCQ (p=0.001) and DCQ (p=0.014). "
Article: Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate
Gene: ATIC
Variant/haplotype: rs4673993
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to methotrexate in people with Arthritis, Rheumatoid as compared to allele T.
Article: IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients
Gene: CYP3A4
Variant/haplotype: rs2242480
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with increased exposure to tacrolimus in people with Kidney Transplantation as compared to genotypes CT + TT.
Notes: This association was seen for time 7, 30, and 90 days after transplantation. Exposure to CC was higher than CT, which was higher than TT.
Article: Tacrolimus Concentration Is Effectively Predicted Using Combined Clinical and Genetic Factors in the Perioperative Period of Kidney Transplantation and Associated with Acute Rejection
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT (assigned as intermediate metabolizer and normal metabolizer phenotype) is associated with decreased dose-adjusted trough concentrations of tacrolimus in people with Kidney Transplantation as compared to genotype CC (assigned as poor metabolizer phenotype) .
Article: The influence of genetic polymorphisms in drug metabolism enzymes and transporters on the pharmacokinetics of different fluvastatin formulations
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): fluvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C9 *1/*3 is associated with increased concentrations of fluvastatin in healthy individuals as compared to CYP2C9 *1/*1.
Notes: The CYP2C9 *3 genotypes were only significantly associated with the AUC 0-24 after the first dose of IR ( P = 0.043), but not significant after repeated doses, or with those in the ER formulation settings.
Article: Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs: A Systematic Review and Meta-Analysis
Gene: CYP2C19
Variant/haplotype: CYP2C19 intermediate metabolizer
Drug(s): phenytoin
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 intermediate metabolizer and poor metabolizer is associated with increased concentrations of phenytoin as compared to CYP2C19 normal metabolizer.
Notes: "We observed 23% (95% CI, 17%-30%) higher phenytoin plasma concentration in CYP2C19 intermediate metabolizers and 39% (95% CI, 24%-56%) higher phenytoin plasma concentration in CYP2C19 poor (Table 3)." "Abolished activity: CYP2C19*2: rs1799853 or CYP2C19*3: rs1057910"
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP2C19
Variant/haplotype: rs12571421
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. This is a proxy SNP for rs4244285 (CYP2C19*2).
Article: Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: not stated
Association: Allele C is associated with dose of warfarin as compared to allele A.
Article: Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients
Gene: ERCC2
Variant/haplotype: rs13181
Drug(s): Platinum compounds
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with increased response to Platinum compounds in people with Carcinoma, Non-Small-Cell Lung as compared to allele T.
Notes: No significant relationship between genotype and drug response was detected.
Article: Genotype-Driven Phase I Study of Irinotecan Administered in Combination With Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): irinotecan
Phenotype category: Dosage
Significant: not stated
Association: UGT1A1 *1/*28 is associated with decreased dose of irinotecan in people with Colorectal Neoplasms as compared to UGT1A1 *1/*1.
Notes: This study provided maximum tolerated doses of irinotecan for the *1/*1 and *1/*28 genotypes. Patients with *28/*28 were excluded. The maximum tolerated doses were found to be considerably higher than the recommended irinotecan dose of 180 mg/m2. Patients with the *1/*28 variant or patients who received >= the maximum tolerated dose had a significantly increased likelihood of complete or partial response (OR=4.35 and OR=5.57, respectively). No significant differences in time to progression (TTP) were seen.
Article: Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron
Gene: HTR3A
Variant/haplotype: rs1062613
Drug(s): granisetron
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is not associated with response to granisetron in healthy individuals as compared to genotypes CT + TT.
Article: Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients
Gene: VEGFA
Variant/haplotype: rs833069
Drug(s): bevacizumab
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to bevacizumab in women with Breast Neoplasms as compared to allele T.
Notes: Please note that alleles have been complemented to the positive strand.
Article: A Genome-Wide Association Study of Citalopram Response in Major Depressive Disorder
Gene: RORA
Variant/haplotype: rs809736
Drug(s): citalopram
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to citalopram in people with Depressive Disorder, Major as compared to allele A.
Notes: It was also associated with remission.  Neither association was significant after correction (430,198 SNPs tested).  Frequencies listed below are for responders vs. nonresponders.  Authors point out the lack of placebo control.
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: rs1051266
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype CC.
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: TT +CT 0.41 (0.09–34.05)) vs. CC (0.59 (0.14–41.63)). Please note: alleles have been complemented to the + chromosomal strand.
Article: Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): anastrozole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A4 *1/*22 (assigned as intermediate metabolizer phenotype) is associated with decreased concentrations of anastrozole in people with Breast Neoplasms and Neoplasm Metastasis as compared to CYP3A4 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: "For CYP3A4, only the CYP3A4*22 variant was identified, and all carriers were heterozygous (CYP3A4*1/*22) and were assigned IM phenotype and CYP3A4 low activity" "In the primary analysis, there was no difference in systemic anastrozole concentrations between low and high CYP3A4 activity phenotype groups (p = 0.13; Table 2 & Figure 1A). However, the posthoc analysis revealed the expected association of low CYP3A4 activity with higher anastrozole concentration in the anastrozole-only arm"
Article: Polymorphisms within the human leucocyte antigen-E gene and their associations with susceptibility to rheumatoid arthritis as well as clinical outcome of anti-tumour necrosis factor therapy
Gene: HLA-E
Variant/haplotype: rs1264457
Drug(s): adalimumab, certolizumab pegol, etanercept, glucocorticoids, infliximab, methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to adalimumab, certolizumab pegol, etanercept, glucocorticoids, infliximab or methotrexate in women with Arthritis, Rheumatoid as compared to genotypes AG + GG.
Notes: Response measured after 12 weeks of treatment. Alleles described as HLA-E *01:03:01 and *01:03:02.
Article: Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure
Gene: CYP2C8
Variant/haplotype: CYP2C8*4
Drug(s): paclitaxel
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C8 *4 is not associated with increased exposure to paclitaxel in women with Breast Neoplasms.
Notes: as measured by time above threshold concentration. CYP2C8*1/*4 or CYP2C8*4/*4 mean = 10.25 h, *1/*1 mean = 11.03 h.
Article: Gamma-glutamyl carboxylase and its influence on warfarin dose
Gene: GGCX
Variant/haplotype: rs11676382
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele G is associated with decreased dose of warfarin as compared to allele C.
Notes: This variant was associated with a 6.1% reduction in warfarin dose per G allele.The clinical impact was modest.
Article: A genome-wide association study of plasma concentrations of warfarin enantiomers and metabolites in sub-Saharan black-African patients
Gene: CYP2C19
Variant/haplotype: rs11188082
Drug(s): warfarin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased metabolism of warfarin in people with Atrial Fibrillation, venous thromboembolism or Heart Valve Diseases as compared to allele A.
Notes: measured as decreased S-warfarin/R-warfarin ratio and using a genome wide significance threshold of < 3.846 × 10−9. Effect direction from supplementary table S14.
Article: Association of a Single-Nucleotide Polymorphism in the Pregnane X Receptor (PXR 63396C→T) with Reduced Concentrations of Unboosted Atazanavir
Gene: NR1I2
Variant/haplotype: rs2472677
Drug(s): atazanavir
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased concentrations of atazanavir in people with HIV Infections as compared to genotypes CC + CT.
Notes: Median Ctrough was lower in individuals with the TT genotype in cohort A (N=47) versus CC+CT genotypes (34 ng/mL [IQR, 25–63 ng/mL] vs. 152 ng/mL (IQR, 47–388 ng/mL; P = .001). In cohort B the TT genotype was also associated with sub-therapeutic ATV concentrations (<150 ng/mL).
Article: Polymorphisms of the µ-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are associated with increased response to ethanol as compared to genotype AA.
Notes: Carriers of the G allele reported significantly higher vigor scores and significantly lower negative mood scores after drinking as compared with AA subjects.
Article: Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota
Gene: CYP1B1
Variant/haplotype: rs1056837
Drug(s): codeine, tramadol
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased clinical benefit to codeine or tramadol in men with Pain as compared to allele G.
Article: Inherited NUDT15 Variant Is a Genetic Determinant of Mercaptopurine Intolerance in Children With Acute Lymphoblastic Leukemia
Gene: TPMT
Variant/haplotype: rs1142345
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: yes
Association: Genotype CC is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CT + TT.
Notes: Decreased dosage was likely to be due to increased toxicity. The authors also calculated a genetic risk score based on genotype at rs1142345 and at rs116855232. Patients who were homozygous wild-type at both SNPs had the lowest genetic risk score and patients who were homozygous for the variant allele at either SNP had the highest genetic risk score. There was an inverse significant association between genetic risk score and dose reduction of mercaptopurine.
Article: Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain
Gene: ARVCF, COMT
Variant/haplotype: rs165728
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Allele T is associated with decreased dose of morphine in people with Neoplasms as compared to allele C.
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, rs2239393, rs4818, rs4680, rs174699, rs740603).  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: NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
Gene: NUDT15
Variant/haplotype: NUDT15*1, NUDT15*2, NUDT15*3, NUDT15*5
Drug(s): acyclovir
Phenotype category: Efficacy
Significant: yes
Association: NUDT15 *2/*2 +*2/*3 +*3/*3 + *5/*5 (assigned as poor metabolizer phenotype) are associated with increased response to acyclovir as compared to NUDT15 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: The degrees of loss of NUDT15 activity is associated with improved anti-CMV effect of acyclovir. Patients with low NUD15 activity in either donor or recipient cells showed the greatest protection against CMV by ACY treatment, with viremia frequency of 20%.
Article: The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*10, CYP2D6*21
Drug(s): aripiprazole
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *1/*1 + *1/*10 (assigned as normal metabolizer phenotype) are associated with decreased metabolism of aripiprazole in healthy individuals also being given paroxetine as compared to CYP2D6 *10/*10 + *10/*21 (assigned as intermediate metabolizer phenotype) .
Notes: The coadministration of paroxetine caused a much larger decrease in aripiprazole metabolism in extensive metabolizers as compared to intermediate metabolizers (CL/F decrease: 58% v 23%; Cmax increase: 39% v 27%; and AUC increase: 140% v 30%; respectively).
Article: Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang
Gene: GGCX
Variant/haplotype: rs2592551
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes AA + AG is associated with increased dose of warfarin in people with Atrial Fibrillation as compared to genotype GG.
Notes: Please note alleles have been complemented to the plus chromosomal strand.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: COMT
Variant/haplotype: rs4633
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele T is associated with decreased response to risperidone in people with Schizophrenia as compared to allele C.
Notes: The T allele was initially significantly more frequent in patients designated as non-responders to risperidone (i.e. <50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.
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: rs209474
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 G.
Article: The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease
Gene: CYP2D6
Variant/haplotype: CYP2D6*17
Drug(s): codeine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *17 is associated with decreased metabolism of codeine in people with Anemia, Sickle Cell.
Notes: Plasma concentrations of the codeine metabolites M3G and M6G were significantly reduced in carriers of this allele, compared to other genotypes examined (non-carriers, *29 and *41 carriers).
Article: Childhood asthma exacerbations and the Arg-16 beta2 receptor polymorphism: a meta-analysis stratified by treatment
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): corticosteroids
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to corticosteroids in children with Asthma as compared to genotype GG.
Article: Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol
Gene: ERCC2
Variant/haplotype: rs1799793
Drug(s): cisplatin, doxorubicin, methotrexate
Phenotype category: Efficacy
Significant: no
Association: Genotypes CT + TT is associated with decreased clinical benefit to cisplatin, doxorubicin and methotrexate in people with Osteosarcoma as compared to genotype CC.
Notes: Alleles complemented. "For ERCC2 rs1799793, 45.2% of patients with the GG genotype presented poor pathological response, compared to 74.3% of patients with the 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: IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection
Gene: IFNL3
Variant/haplotype: rs11881222
Drug(s): peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG is associated with decreased response to peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotype AA.
Notes: This genotype has decreased association with sustained virological response (SVR).
Article: Smoking Cessation Pharmacogenetics: Analysis of Varenicline and Bupropion in Placebo-Controlled Clinical Trials
Gene: HYKK
Variant/haplotype: rs7164594
Drug(s): varenicline
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT are associated with increased response to varenicline in people with Tobacco Use Disorder as compared to genotype CC.
Notes: Patients with the CT or TT genotypes were more likely to have quit smoking in weeks 9-12 of varenicline treatment. However, this association was not seen when smoking abstinence up to week 52 of follow-up was analyzed.
Article: Pharmacogenetics of Antiepileptic Drug Efficacy in Childhood Absence Epilepsy
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): lamotrigine
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased clinical benefit to lamotrigine in children with Epilepsy as compared to allele C.
Notes: as measured by minor allele frequency in not–seizure‐free vs seizure-free children. Alleles complemented to plus chromosomal strand.