shlokn/autogkb huggingface dataset:
Article: Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*17
Drug(s): sertraline
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2C19 *17/*17 (assigned as ultrarapid metabolizer phenotype) is associated with increased metabolism of sertraline as compared to CYP2C19 *1/*1 (assigned as normal metabolizer phenotype) .
Notes: Among CYP2C19 UMs, the mean estimated serum concentration of both sertraline and N-desmethylsertraline was 10% lower compared to NMs (p = 0.012 and p = 0.016, respectively). No significant difference in metabolic ratio between UMs and NMs was observed (p = 0.517). The OR for having =1 TDM measurements below the target concentration range of 30 nM in CYP2C19 UMs was 1.31 (p = 0.098, CI: 0.95–1.80) compared to NMs.
Article: Impact of the Superoxide Dismutase 2 Val16Ala Polymorphism on the Relationship between Valproic Acid Exposure and Elevation of γ-Glutamyltransferase in Patients with Epilepsy: A Population Pharmacokinetic-Pharmacodynamic Analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): valproic acid
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2C9 *3 is not associated with clearance of valproic acid in people with Epilepsy as compared to CYP2C9 *1.
Notes: Clearance here refers to apparent oral clearance as assayed by serum concentration of valproic acid (VPA) (micrograms/ml). The authors used NONEM to assess serum concentration of VPA.
Article: A prospective study to assess the association between genotype, phenotype and Prakriti in individuals on phenytoin monotherapy
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): phenytoin
Phenotype category: Toxicity
Significant: no
Association: CYP2C19 *1/*2 is not associated with increased concentrations of phenytoin in people with Epilepsy as compared to CYP2C19 *1/*1.
Notes: Concentrations were assessed in relation to toxic concentrations of phenytoin compared to *1/*1.
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, CYP2A6*46
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2A6 *1/*2 + *1/*4 + *1/*9 + *1/*12 + *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 (assigned as intermediate and low activity phenotype) are associated with decreased metabolism of nicotine as compared to CYP2A6 *1/*1 +*1/*46 + *46/*46 (assigned as normal metabolizer phenotype) .
Notes: Please note that the *46 allele is described as the *1B1 allele in the paper and has subsequently been reassigned by PharmVar.
Article: A Physiologically Based Pharmacokinetic Approach to Recommend an Individual Dose of Tacrolimus in Adult Heart Transplant Recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *3/*3 is associated with decreased clearance of tacrolimus in people with heart transplantation as compared to CYP3A5 *1/*1 + *1/*3.
Notes: "the apparent clearance was 12.2 ± 6.0 L/h for CYP3A5*3*3, while it was 27.3 ± 11.5 L/h for individuals with at least one CYP3A5*1 allele (p < 0.001). The results are shown in Figure 1."
Article: Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17
Drug(s): praziquantel
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 + *1/*3 is associated with increased exposure to praziquantel in children with Schistosomiasis as compared to CYP2C19 *1/*1 + *1/*17.
Article: Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): buprenorphine
Phenotype category: Dosage
Significant: no
Association: Genotype CT is associated with increased dose of buprenorphine in people with Opioid-Related Disorders.
Notes: Case study of a patient receiving buprenorphine/naloxone as opioid agonist treatment. Patient experienced withdrawal symptoms when dose was reduced from 28mg/day to 24mg/day, indicating a potential ultrarapid metabolizer phenotype. Authors state "The patient was determined to exhibit the CYP3A4*1/*1B genotype"
Article: CFTR modulators response of S737F and T465N CFTR variants on patient-derived rectal organoids
Gene: CFTR
Variant/haplotype: rs186089140
Drug(s): elexacaftor / tezacaftor / ivacaftor
Phenotype category: PD
Significant: no
Association: Allele T is associated with increased clinical benefit to elexacaftor / tezacaftor / ivacaftor.
Notes: Functional evaluation of modulator treatment on rectal organoids derived from subjects 1 and 2 carrying the S737F/W1282X and S737F/Dele22-24 genotype"Here, we analyzed two of these subjects for which intestinal organoids were available, and we demonstrated that a trend to respond to ETI treatment was present but appeared prominent only in one of the subjects presenting the lowest residual function, while it was reported as significant in nasal cells." ETI induced a modest increase in CFTR function, which resulted in more evidence for the case carrying the S737F/Dele22-24 genotype.
Article: Relationship of cytochrome P450 gene polymorphisms with blood concentrations of hydroxychloroquine and its metabolites and adverse drug reactions
Gene: CYP3A4
Variant/haplotype: rs3735451
Drug(s): hydroxychloroquine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CC is associated with decreased concentrations of hydroxychloroquine in people with Arthritis, Rheumatoid or Lupus Erythematosus, Systemic as compared to genotypes CT + TT.
Notes: Authors state "We found that CYP3A4 (rs3735451) was significantly correlated with blood concentration of HCQ and its metabolites by adjusting for the time of administration, and the mean blood concentrations of HCQ, DHCQ, and DCQ in patients with CC, CT, and TT genotypes is higher than those of other genotypes, with the blood concentration of HCQ and its main metabolite DHCQ being the lowest for the CC genotype."
Article: G-Protein-Coupled Receptor Kinase 4 Polymorphisms and Blood Pressure Response to Metoprolol Among African Americans: Sex-Specificity and Interactions
Gene: GRK4
Variant/haplotype: rs2960306
Drug(s): metoprolol
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with decreased response to metoprolol in women with hypertensive nephrosclerosis as compared to genotype GG.
Notes: Response was measured by time to reach a mean arterial pressure of < or = 107 mm Hg.
Article: Genome-wide study of methotrexate clearance replicates SLCO1B1
Gene: SLCO1B1
Variant/haplotype: rs11045879
Drug(s): methotrexate
Phenotype category: Efficacy, Toxicity, Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele T.
Article: Genetic Association of Olanzapine Treatment Response in Han Chinese Schizophrenia Patients
Gene: DRD3
Variant/haplotype: rs324026
Drug(s): olanzapine
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased clinical benefit to olanzapine in people with Schizophrenia as compared to allele T.
Notes: Authors state "individuals with C alleles of rs324026 generally experience significantly better efficacy of OLA treatment."
Article: Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies
Gene: MTHFR
Variant/haplotype: rs1801131
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with decreased response to methotrexate in children with Lymphoma, Non-Hodgkin or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes GG + GT.
Notes: Patients with the TT genotype had significantly better relapse-free survival. Please note that alleles have been complemented to the positive strand.
Article: The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with metabolism of tacrolimus in children with liver transplantation as compared to genotype CC.
Notes: In pediatric liver transplantation recipients, CYP3A5 genotype was not associated with tacrolimus dose, meadian tacrolimus concentration and lower C/D ratios.
Article: Lumacaftor/Ivacaftor in Patients Aged 6–11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor, lumacaftor
Phenotype category: Efficacy
Significant: no
Association: Genotype del/del is not associated with response to ivacaftor and lumacaftor in children with Cystic Fibrosis.
Notes: F508del allele. No significant change in ppFEV1 observed following 24 weeks of lumacaftor treatment.
Article: Interaction between the μ-opioid receptor gene and the number of heavy drinking peers on alcohol use
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Other
Significant: no
Association: Allele G is not associated with dose of ethanol as compared to allele A.
Notes: No significant main effect of this variant or interaction effect between this variant and social drinking condition on alcohol consumption in a controlled setting or blood alcohol content.
Article: A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts
Gene: C11orf65
Variant/haplotype: rs11212617
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased clinical benefit to metformin in people with Diabetes Mellitus, Type 2 as compared to allele A.
Article: Pharmacokinetic-Pharmacodynamic interaction associated with venlafaxine-XR remission in patients with major depressive disorder with history of citalopram / escitalopram treatment failure
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer phenotype
Drug(s): duloxetine
Phenotype category: Efficacy
Significant: no
Association: CYP2D6 poor metabolizer is not associated with response to duloxetine as compared to CYP2D6 normal metabolizer and intermediate metabolizer.
Notes: In patients with no remission to citalopram or escitalopram treatment, duloxetine remission rates were not significantly different between CYP2D6 UM, IM/NM or PM.
Article: Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery
Gene: UGT2B7
Variant/haplotype: rs10028494
Drug(s): fentanyl
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of fentanyl in people with Pain, Postoperative as compared to allele C.
Notes: There was no significant difference in 24 hour fentanyl use between the genotype groups.
Article: Association between imatinib transporters and metabolizing enzymes genotype and response in newly diagnosed chronic myeloid leukemia patients receiving imatinib therapy
Gene: ABCB1
Variant/haplotype: rs3213619
Drug(s): imatinib
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotypes AG + GG.
Notes: This genotype was not significantly with associated with likelihood of achieving complete molecular response (CMR) within 12 months. CMR was classified based on BCR-ABL to control gene transcript ratios, expressed on the International Scale; CMR was a ratio <= 0.0032%.
Article: Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma
Gene: ABCG2
Variant/haplotype: rs2231142
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased metabolism of methotrexate in children with Osteosarcoma as compared to allele G.
Notes: The T allele is associated with longer half-life of methotrexate.
Article: Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study
Gene: NR1I3
Variant/haplotype: rs3003596
Drug(s): (R)-methadone
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype GG is associated with increased clearance of (R)-methadone in people with HIV Infections.
Notes: "Being HIV+, taking ART, presence of the rare ABCB1 rs2032582 T allele, and combined presence of the NR1I3 rs2307424 GG and rs3003596 GG genotypes if taking EFV each significantly increased R-methadone CL/F."
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: NR1I2
Variant/haplotype: rs3814055
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.
Article: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform
Gene: CHST3
Variant/haplotype: rs4148943
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 data in pgkb, actual base not listed in paper)
Article: Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV
Variant/haplotype: rs11995962
Drug(s): tenofovir
Phenotype category: Metabolism/PK
Significant: no
Association: Allele T is not associated with clearance of tenofovir in people with HIV Infections as compared to allele C.
Notes: Significance threshold was set at 5.0E-9.
Article: CYP3A4*1B but Not CYP3A5*3 as Determinant of Long-Term Tacrolimus Dose Requirements in Spanish Solid Organ Transplant Patients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: not stated
Association: Genotype CC is associated with increased concentrations of tacrolimus in people with Transplantation as compared to genotype CT.
Notes: Transplants included 14 hepatic, 9 renal, 2 cardiac and one pulmonary (from table 1). Alleles complemented. CYP3A5*3/*3 CYP3A4*1/*1 had higher dose adjusted blood concentrations compared to CYP3A5*3/*1 CYP3A4*1/*1B. Concentrations were only measured in 9 patients. CYP3A5*3/*3 is rs776746 CC, there were no *1/*1
Article: Association of TLR 9 gene polymorphisms with remission in patients with rheumatoid arthritis receiving TNF-α inhibitors and development of machine learning models
Gene: TLR9
Variant/haplotype: rs352139
Drug(s): adalimumab, etanercept, infliximab, Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with increased response to adalimumab, etanercept, infliximab or Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid as compared to genotype CC.
Notes: Authors report variant as significantly associated with remission, and define remission as "DAS-28 score of less than 2.6 after 6 months of TNF-α inhibitor therapy."
Article: An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function
Gene: CYP2D6
Variant/haplotype: CYP2D6 intermediate metabolizer
Drug(s): primaquine 5,6-orthoquinone
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 intermediate metabolizer is associated with decreased concentrations of primaquine 5,6-orthoquinone in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: "For urine data... The normalized total CAE of POQ was significantly lower in CYP2D6 IM than in CYP2D6 NM (115 (46–297) vs. 318 (92–498) μg/mg/kg, respectively, p = 0.047, Table 3, Fig. 2, Fig. 3B). " POQ = primaquine 5,6-orthoquinone
Article: Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients
Gene: EXO1
Variant/haplotype: rs1047840
Drug(s): capecitabine, fluorouracil
Phenotype category: Efficacy
Significant: not stated
Association: Allele A is associated with increased response to capecitabine or fluorouracil in people with Neoplasm Metastasis as compared to allele G.
Notes: pfSNP identified 2800 SNPS associated with key-words: 5-FU, capecitabine and oxilaplatin and colorectal cancer. Various criteria were used to determine 1536 SNPs to genotype. These SNPs were genotyped in a discovery cohort (N=62) and tested in a validation cohort (N=27). Both cohorts consisted of patients with colorectal cancer metastasis in liver. Five SNPs (rs2289310 G>T; rs1047840 G>A;  rs17431184 T>C; rs17160359 G>T; rs2236722 A>G)  were identified as distinguishing the "non-responder" phenotype from the "responder" phenotype when using a logistic regression multivariate model. The AUC for the receiver operating characteristic curve of the 5 SNPs is 0.875. This logistic-based multivariate model is said to be able to identify 39.1% of non-responders.
Article: Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin
Gene: SLC2A2
Variant/haplotype: rs8192675
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to metformin in people with Diabetes Mellitus as compared to allele T.
Notes: The C allele of rs8192675 was associated with a 0.17% (P = 6.6 × 10-14) greater metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of European ancestry.
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs2234918
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele C.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.
Article: A single low dose of primaquine is safe and sufficient to reduce transmission of Plasmodium falciparum gametocytes regardless of cytochrome P450 2D6 enzyme activity in Bagamoyo district, Tanzania
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizers and intermediate metabolizers
Drug(s): primaquine
Phenotype category: Efficacy
Significant: no
Association: CYP2D6 poor metabolizers and intermediate metabolizers is not associated with decreased clinical benefit to primaquine in children with Malaria as compared to CYP2D6 normal metabolizer.
Notes: CYP2D6 was assessed using "mass array VeriDose CYP2D6 CNV Panel". Authors group PM and IM as "reduced CYP2D6 activity" and was 33/157 individuals, 3 individuals were increased activity. "none of the patients had parasitaemia on day 3"
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: ARSA
Variant/haplotype: rs2071421
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: Pharmacogenetic Predictors of Cannabidiol Response and Tolerability in Treatment‐Resistant Epilepsy
Gene: ABCC5
Variant/haplotype: rs3749442
Drug(s): cannabidiol
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with decreased response to cannabidiol in people with Epilepsy as compared to genotype GG.
Article: Novel CYP2A6 variants identified in African Americans are associated with slow nicotine metabolism in vitro and in vivo
Gene: CYP2A6
Variant/haplotype: rs376817657
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with decreased metabolism of nicotine as compared to genotype CC.
Notes: Association with lower activity of the novel variant groups [CYP2A6*39 (V68M), CYP2A6*40 (I149M), CYP2A6*41 (R265Q), CYP2A6*42 (I268T), CYP2A6*43 (T303I), CYP2A6*44 (E390K; rs376817657), CYP2A6*44 (L462P)] was; tested using a one-way analysis of variance with Bonferroni tests used for post-hoc analysis, P<0.01. A comparison between CYP2A6*1/*1 and; the combined group was tested using an unpaired t-test, ***P<0.001
Article: Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): lumefantrine
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to lumefantrine in women with Malaria and Pregnancy as compared to allele C.
Article: Cholinergic receptor nicotinic alpha 5 subunit polymorphisms are associated with smoking cessation success in women
Gene: CHRNB3
Variant/haplotype: rs6474413
Drug(s): bupropion, nicotine, varenicline
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to bupropion, nicotine or varenicline in people with Tobacco Use Disorder as compared to allele C.
Notes: No significant effect of genotype on likelihood of being abstinent from smoking at 6 months after starting pharmacotherapy for smoking cessation. Please note that alleles have been complemented to the positive strand.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: GRIK3
Variant/haplotype: rs6691840
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele A.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Previously reported PDE3A–SLCO1C1 genetic variant does not correlate with anti-TNF response in a large UK rheumatoid arthritis cohort
Gene: SLCO1C1
Variant/haplotype: rs3794271
Drug(s): Tumor necrosis factor alpha (TNF-alpha) inhibitors
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to Tumor necrosis factor alpha (TNF-alpha) inhibitors in people with Arthritis, Rheumatoid.
Notes: as measured by either EULAR or change in DAS28