shlokn/autogkb huggingface dataset:
Article: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
Gene: PPARD
Variant/haplotype: rs2016520
Drug(s): docetaxel, thalidomide
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to docetaxel and thalidomide in people with Prostatic Neoplasms as compared to allele T.
Notes: (allele inferred by frequency comparison with dbSNP, actual base not listed in paper, dbSNP changed designation of this allele from G/A to C/T at build 132)
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: SLCO1B1
Variant/haplotype: rs11045879
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CC + CT are not associated with concentrations of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype TT.
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: CC +TC (0.50 (0.09–41.63)) vs. TT(0.39 (0.12–19.88))
Article: PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis
Gene: PDE4D
Variant/haplotype: rs295943
Drug(s): apremilast
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased clinical benefit to apremilast in people with Psoriasis as compared to allele C.
Notes: "Allele-based association tests detected 64 SNPs displaying nominal p values < 0.05 (Table 2) including 10 SNPs with p values ≤ 0.01. " Table 2 shows frequency of minor allele is responders and non-responders. Responder status maybe defined by PASI score improvement greater than 75% after 24–36 weeks of treatment.
Article: Genomic Association Analysis Reveals Variants Associated With Blood Pressure Response to Beta‐Blockers in European Americans
Gene: SLC4A1
Variant/haplotype: rs45545233
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT are associated with decreased response to atenolol or metoprolol in people with Hypertension as compared to genotype TT.
Notes: The grouped CC and CT genotypes were associated with a smaller decrease in diastolic blood pressure in a meta-analysis of patients receiving metoprolol or atenolol monotherapy (discovery cohort) and in patients receiving atenolol addon therapy (replication cohort).
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: HRH4
Variant/haplotype: rs4483927
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to risperidone in people with Schizophrenia as compared to allele T.
Article: ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
Gene: ADH1C
Variant/haplotype: rs283416
Drug(s): ethanol
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Allele A is associated with metabolism of ethanol.
Notes: The authors did not report p-value correction for multiple hypotheses (103 snps tested).  Though they report multiple snps are significantly associated with alcohol metabolism (early or late) tested on blood or breath alcohol concentrations, this snp is NOT significant after Bonferroni correction (<0.00049).  Also, the authors did not state which alleles are associated with increased or decreased metabolism.  Instead, they simply report an association with the snp in general.  Note that this gene is on the minus strand.
Article: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*3, CYP3A4*20, CYP3A4*22
Drug(s): fesoterodine
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP3A4 *3 + *20 + *22 are associated with increased clearance of fesoterodine in healthy individuals as compared to CYP3A4 *1.
Notes: Clearance was increased in the presence of CYP3A4 variants. Statistical analysis was not carried out for individual drugs due to the low number of subjects carrying CYP3A4 variants. *3 allele was identified using rs4986910, *20 was identified using rs67666821 and *22 was identified using rs35599367.
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: rs2838958
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes AG + GG.
Notes: Although this variant showed a trend of association with response, it was not associated in univariate analysis, but subsequent inclusion in a Cox multivariable regression analysis.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: SLC29A4
Variant/haplotype: rs10234709
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
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 rs10234709 as top SNP for SLC29A4
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: rs1056836
Drug(s): codeine, tramadol
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with decreased clinical benefit to codeine or tramadol in men with Pain as compared to allele G.
Article: Relationship between Genotypes Sult1a2 and Cyp2d6 and Tamoxifen Metabolism in Breast Cancer Patients
Gene: SULT1A2
Variant/haplotype: rs1059491
Drug(s): 4-hydroxytamoxifen, endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT are associated with decreased concentrations of 4-hydroxytamoxifen or endoxifen in women with Breast Neoplasms as compared to genotypes GG + GT.
Notes: as part of haplotype *1*1 vs *1/*2 + *2/*2 (rs1136703A>G and rs1059491T>G). Pre and postmenopausal woman with estrogen receptor-positive breast cancer undergoing tam treatment after surgery and chemotherapy/radiation. Patients were excluded if tamoxifen therapy was started with either chemotherapy or radiation.
Article: Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta‐Analysis
Gene: SLC47A1
Variant/haplotype: rs2289669
Drug(s): metformin
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele G.
Notes: This variant is not associated with metformin glycemic response assessed as HbA1c reduction in patients on metformin monotherapy.
Article: Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4‐hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus
Gene: CYP2B6
Variant/haplotype: rs7254579
Drug(s): cyclophosphamide
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with metabolism of cyclophosphamide in people with Lupus erythematosus as compared to allele T.
Notes: This SNP had a small but significant effect on cyclophosphamide (CPA) metabolite plasma concentrations (4-OH-CPA), but not on CPA concentrations (Bonferroni corrected p-value= 0.0056).
Article: Response Prediction in Chronic Hepatitis C by Assessment of IP-10 and IL28B-Related Single Nucleotide Polymorphisms
Gene: IFNL3, IFNL4
Variant/haplotype: rs12979860
Drug(s): peginterferon alfa-2a, peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C as compared to genotypes CT + TT.
Notes: Significantly lower baseline plasma levels of IP-10 were associated with this SNP. Lower levels of IP-10 were found to be statistically significantly associated with better treatment outcome. This SNP was found to be in strong linkage disequilibrium with rs8099917.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: IL18
Variant/haplotype: rs5744247
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele G.
Notes: This study was attempting to validate reported variants and tacrolimus trough concentration in a large population of African American and European American kidney transplant patients.
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP3A5
Variant/haplotype: CYP3A5 poor metabolizer and intermediate metabolizer genotypes
Drug(s): N-desmethyltamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of n-desmethyltamoxifen in women with Breast Neoplasms.
Article: A Longitudinal HbA1c Model Elucidates Genes Linked to Disease Progression on Metformin
Gene: CSMD1
Variant/haplotype: rs2617102
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AC + CC is associated with decreased response to metformin in people with Diabetes Mellitus as compared to genotype AA.
Notes: using computational model-based approaches and genetic, demographic, and long-term HbA1c data from 1,056 patients.
Article: Population Pharmacokinetic−Pharmacodynamic Modeling of Carvedilol to Evaluate the Effect of Cytochrome P450 2D6 Genotype on the Heart Rate Reduction
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*10
Drug(s): carvedilol
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *10/*10 is associated with decreased clearance of carvedilol in healthy individuals as compared to CYP2D6 *1/*1 + *1/*2.
Notes: "This population PK−PD analysis also showed that CYP2D6*10/*10 subjects had a 32.7% lower carvedilol CL/F than CYP2D6*1/*1 and *1/*2 subjects."
Article: Assessing the clinical impact of CYP2C9 pharmacogenetic variation on phenytoin prescribing practice and patient response in an integrated health system
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3
Drug(s): phenytoin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*3 + *2/*2 + *2/*3 + *3/*3 are associated with decreased dose of phenytoin as compared to CYP2C9 *1/*1.
Notes: Low-intermediate/poor CYP2C9 genotype was associated with greater odds of having a lower dose by the end of the first year of treatment in the full cohort (OR 1.11; 95% CI: 1.02–1.22; P=0.02).
Article: Pharmacogenetics of TNF inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score
Variant/haplotype: rs12081765
Drug(s): adalimumab, certolizumab pegol, etanercept, infliximab, Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with increased response to adalimumab, certolizumab pegol, etanercept, infliximab or Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to allele A.
Notes: as measured by change in 2C-DAS28. Table 2 shows change was a negative value for this variant suggesting decreased 2C-DAS28 and increased response, it was not attributed to a particular allele at this rs number location so assumed minor allele based on dbSNP.
Article: Impact of Viloxazine Extended-Release Capsules (Qelbree®) on Select Cytochrome P450 Enzyme Activity and Evaluation of CYP2D6 Genetic Polymorphisms on Viloxazine Pharmacokinetics
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer
Drug(s): viloxazine
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 poor metabolizer is associated with increased exposure to viloxazine in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: "The increase in peak and total exposures for CYP2D6 PMs generally fell within the pharmacokinetic variability of CYP2D6 EMs, and the differences observed in PMs are not considered to be clinically relevant."
Article: CYP3A5 Gene Variation Influences both Systemic and Intrarenal Tacrolimus Disposition
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*6
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*1 + *1/*6 is associated with increased clearance of tacrolimus in healthy individuals as compared to CYP3A5 *6/*6.
Notes: Healthy individuals with the CYP3A5 *1/*1 or *1/*6 (rs10264272) genotype had 1.6-fold higher oral tacrolimus clearance and 2.0 - 2.7-fold higher metabolite/parent area under the curve (AUC) ratios for 31-desmethyl tacrolimus (31-DMT), 12-hydroxytacrolimus, and 13-desmethyl tacrolimus (13-DMT), as compared to individuals with the *6/*6 genotype. Subjects who carry two copies of loss-of-function CYP3A5 alleles (CYP3A5*3/rs776746, CYP3A5*6 or CYP3A5*7/rs41303343) were pooled together as CYP3A5 non-expressors for this analysis. CYP3A5 *1 allele carriers were pooled togethers as CYP3A5 expressors.
Article: A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit/Hyperactivity Disorder
Gene: SNAP25
Variant/haplotype: rs3746544
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 T.
Article: Initial Evidence that Oprm1 Genotype Moderates Ventral and Dorsal Striatum Functional Connectivity During Alcohol Cues
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Efficacy
Significant: not stated
Association: Genotype AG is associated with increased response to ethanol in people with Alcoholism as compared to genotype AA.
Notes: MRI study. Participants with the AG genotype had increased activation within regions including the right insula, bilateral supramarginal gyri, left precuneus, right superior parietal lobule, right orbitofrontal cortex and right angular gyrus following an alcohol cue than AA participants.
Article: Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives – Results from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study
Gene: SH2B3
Variant/haplotype: rs3184504
Drug(s): hydrochlorothiazide
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to hydrochlorothiazide in people with Hypertension as compared to allele T.
Notes: Not significant when using Bonferroni-corrected alpha of 0.0014. Response was assessed by change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 9 weeks of treatment.
Article: Association of CYP2C19*2 and associated haplotypes with lower norendoxifen concentrations in tamoxifen‐treated Asian breast cancer patients
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): tamoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *2 is associated with decreased metabolism of tamoxifen in women with Breast Neoplasms as compared to CYP2C19 *1.
Notes: The authors measured levels of tamoxifen and its metabolites (N-desmethyltamoxifen (NDM), (Z)-4-hydroxytamoxifen, (Z)-endoxifen, N,N-Didesmethyltamoxifen (NDDM)) in women with estrogen receptor + breast cancer. Women carried a CYP2C19 *2 allele had significantly lower nor-endoxefin (NorEND) levels (P<0.001), as well as a lower metabolic ratio (MR) of NorEND/(Z)-END (P<0.001) and a lower MR of NorEND /NDDM (P<0.001) as compared to women with the CYP2C19 *1/*1 genotype even after adjusting for age and CYP2D6 metabolizer status.
Article: CYP3A5, ABCB1 and SLCO1B1 Polymorphisms and Pharmacokinetics and Virologic Outcome of Lopinavir/Ritonavir in HIV-infected Children
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): lopinavir, ritonavir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with response to lopinavir or ritonavir in children with HIV Infections as compared to allele C.
Notes: No association between this variant and virologic suppression in patients treated with lopinavir/ritonavir. Variant referred to in the paper as G2677T.
Article: Effects of CYP3A4*22 polymorphism on trough concentration of tacrolimus in kidney transplantation: a systematic review and meta-analysis
Gene: CYP3A4
Variant/haplotype: CYP3A4*1, CYP3A4*22
Drug(s): tacrolimus
Phenotype category: Dosage
Significant: yes
Association: CYP3A4 *1/*22 + *22/*22 is associated with decreased dose of tacrolimus in people with Kidney Transplantation as compared to CYP3A4 *1/*1.
Notes: "Therefore, the significant effect of CYP3A4*22 on C0/D and the dose requirement of Tac remained evident even after adjusting for CYP3A5*3."
Article: SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): capecitabine, fluorouracil, irinotecan, leucovorin
Phenotype category: Efficacy
Significant: no
Association: Genotypes CC + CT are not associated with increased response to capecitabine, fluorouracil, irinotecan or leucovorin in people with Colorectal Neoplasms as compared to genotype TT.
Notes: Patients were split into two groups based on treatment. One group received irinotecan, fluorouracil, and leucovorin, and the other group received irinotecan and capecitabine. No association was found between this SNP and rapid response rate, progression free survival, or irinotecan-related time to treatment failure.
Article: Stress and Bronchodilator Response in Children with Asthma
Variant/haplotype: rs34548976
Drug(s): adrenergics, inhalants
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to adrenergics, inhalants in children with Asthma as compared to allele C.
Notes: For the discovery cohort, 351 children (ages 6–14 yr) with asthma (defined as physician-diagnosed asthma and =1 episode of wheeze in the previous yr) were recruited from households in San Juan (Puerto Rico). Replication of our findings for stress and BDR was attempted in 471 children with asthma (ages 7–15 yr) living in Rhode Island (n=229; 59 PR, 81 Dominican, and 89 non-Hispanic white children) and Puerto Rico (n=242) (Rhode Island Puerto Rico Asthma Center [RIPRAC] cohort). Finally, children with high child anxiety and BDR were assessed in 87 children (ages 12–17 yr) in the National Health and Nutrition Examination Survey (NHANES) in 2007–2010.
Article: Association of CCND1 rs9344 polymorphism with lung cancer susceptibility and clinical outcomes: a case-control study
Gene: CCND1
Variant/haplotype: rs9344
Drug(s): pemetrexed, Platinum compounds
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with increased clinical benefit to pemetrexed and Platinum compounds in people with Lung Neoplasms as compared to allele G.
Notes: "However, CCND1 rs9344 was found to be significantly correlated with the platinum-based chemotherapy response of patients who received platinum + pemetrexed therapy (additive model: adjusted OR = 1.926, 95%CI = 1.029–3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428–90.100, P = 0.022)."
Article: Influence of Polymorphisms in the HTR3A and HTR3B Genes on Experimental Pain and the Effect of the 5-HT3 Antagonist Granisetron
Gene: HTR3B
Variant/haplotype: rs1176744
Drug(s): granisetron
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to granisetron in healthy individuals as compared to genotypes AC + CC.
Article: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol
Gene: HLA-C
Variant/haplotype: rs9366772
Drug(s): allopurinol
Phenotype category: Efficacy
Significant: no
Association: Allele A is associated with increased 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: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: ABCB1
Variant/haplotype: rs4148738
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with trough concentration of tacrolimus in people with Kidney Transplantation and Transplantation as compared to allele C.
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 for rs2032582 (2677G/T/A ).
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: rs292449
Drug(s): atenolol
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to atenolol in people with Hypertension as compared to allele G.
Article: Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes
Gene: KCNQ1
Variant/haplotype: rs2237895
Drug(s): gliclazide
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased clinical benefit to gliclazide in people with Diabetes Mellitus, Type 2 as compared to allele A.
Notes: "Similarly, the rs2237895 C allele was associated with a 2.360-fold decrease in glycated hemoglobin compared with the A allele (95% CI: 1.225–4.550, P=0.009)."
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: HRH3
Variant/haplotype: rs3787429
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to risperidone in people with Schizophrenia as compared to allele C.
Article: Pharmacogenetics of 6-mercaptopurine in a black Zimbabwean cohort treated for acute lymphoblastic leukaemia
Gene: TPMT
Variant/haplotype: TPMT*1, TPMT*3C
Drug(s): mercaptopurine
Phenotype category: Dosage
Significant: no
Association: TPMT *1/*3C is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to TPMT *1/*1.
Notes: "The median 6-MP dose intensity was considerably low (47%) among TPMT*1/*3C individuals (n = 4) compared with TPMT*1/*1 (77%) individuals (n = 19)" "TPMT*3C. Other TPMT alleles *2, *3A and *3B were not detected in this study. The NUDT15*1 allele was detected at a frequency of 100%."
Article: Influence of pharmacogenetic polymorphisms and demographic variables on metformin pharmacokinetics in an admixed Brazilian cohort
Gene: SLC22A1
Variant/haplotype: rs1867351
Drug(s): metformin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with exposure to metformin as compared to allele T.
Article: Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients
Gene: CALU
Variant/haplotype: rs1043550
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of warfarin as compared to allele A.