shlokn/autogkb huggingface dataset:
Article: No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV‐1–Infected Subjects
Gene: CYP3A5
Variant/haplotype: CYP3A5 intermediate metabolizers
Drug(s): maraviroc
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 intermediate metabolizer is associated with increased concentrations of maraviroc in people with HIV Infections as compared to CYP3A5 normal metabolizer.
Notes: In study A4001110, black CYP3A5 intermediate metabolizers had a significant increase in average maraviroc plasma concentrations compared to black extensive metabolizers. The authors determined this difference in maraviroc concentrations to not be clinically significant.
Article: An integrated pharmacokinetic/pharmacogenomic analysis of ABCB1 and SLCO1B1 polymorphisms on edoxaban exposure
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): edoxaban
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with exposure to edoxaban in healthy individuals as compared to genotypes AG + GG.
Notes: No significant difference in total plasma exposure (AUCinf), peak plasma exposure (Cmax), trough concentrations (C24), plasma exposure from the time of dosing to the last measurable concentration (AUClast), or plasma exposure up to 24 hours after dosing (AUC0-24) were seen between any of the genotypes. This indicates that this SNP "does not significantly affect edoxaban exposure".
Article: Anastrozole Aromatase Inhibitor Plasma Drug Concentration Genome‐Wide Association Study: Functional Epistatic Interaction Between SLC38A7 and ALPPL2
Variant/haplotype: rs11648166
Drug(s): anastrozole
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele G is associated with increased concentrations of anastrozole in women with Breast Neoplasms as compared to allele A.
Notes: The minor allele of this variant was associated with increased plasma concentrations of anastrozole in postmenopausal women with ER+ breast cancer.
Article: Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians
Gene: NR1I2
Variant/haplotype: rs2472677
Drug(s): nevirapine
Phenotype category: Dosage, Metabolism/PK
Significant: no
Association: Genotypes CT + TT are not associated with decreased clearance of nevirapine in people with HIV Infections as compared to genotype CC.
Notes: no association with PK parameters area under the concentration time curve or apparent oral clearance of the drug. [stat_test: univariate and multiple linear regression]
Article: A randomized placebo-controlled trial of ataluren for the treatment of nonsense mutation cystic fibrosis
Gene: CFTR
Variant/haplotype: rs113993959
Drug(s): ataluren
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to ataluren in people with Cystic Fibrosis as compared to allele G.
Notes: Outcomes assessed for all nonsense mutations together (W1282X, G542X, R1162X, and R553X). Case-control study with placebo. Endpoint measured was change in Forced Expiratory Volume in 1 second. A difference was seen in the subset of patients on tobramycin.
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: rs1024323
Drug(s): metoprolol
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to metoprolol in men with hypertensive nephrosclerosis as compared to genotype TT.
Notes: This was an additive effect - patients with the CT genotype had a worse response compared to those with TT but better response compared to those with CC. Using Cox analysis, this was shown to only be significant in men who were also heterozygous or homozygous for the rs2960306 allele T (Leu65) and was not seen in men homozygous for rs2960306 allele G (Arg65). Response was measured by time to reach a mean arterial pressure of < or = 107 mm Hg.
Article: The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation
Gene: DTNBP1
Variant/haplotype: rs909706
Drug(s): haloperidol
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is associated with increased response to haloperidol in people with Schizophrenia as compared to genotype CC.
Notes: [Drug: clozapine]
Article: TPMT Genetic Variations in Populations of the Russian Federation
Gene: TPMT
Variant/haplotype: TPMT*1, TPMT*2, TPMT*3A, TPMT*3C
Drug(s): methotrexate, purine analogues
Phenotype category: Efficacy
Significant: no
Association: TPMT *1/*2 + *1/*3A + *1/*3C is not associated with response to methotrexate and purine analogues in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to TPMT *1/*1.
Notes: Event Free Survival: 90% for heterozygotes;83% for *1/*1 at median followup of 31.3 months (range 4-163 months).  The assay used detects *2,*3A,*3B,*3C,*3D,*7 and *8. Treatment protocol ALL BFM-90 or ALL MB-91/2002 was followed.  In the group of pediatric cancer patients (a superset of the ALL patients), frequencies of the total number of "variant" alleles were: *2: 6.1%; *3A: 81.8%; *3C: 12.1% .
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs1303839356
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele T is associated with decreased metabolism of nicotine as compared to allele C.
Notes: Assigned as loss-of-function following in vitro assessments, in vivo associations and variant construct functional assignments. Please note that alleles have been complemented to the positive strand.
Article: Polymorphisms of MTHFR Associated with Higher Relapse/Death Ratio and Delayed Weekly MTX Administration in Pediatric Lymphoid Malignancies
Gene: MTHFR
Variant/haplotype: rs1801133
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in children with Lymphoma, Non-Hodgkin or Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele G.
Notes: No significant difference in relapse-free survival between genotype groups. Please note that alleles have been complemented to the positive strand.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRD1
Variant/haplotype: rs1042114
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele T.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy. Please note that alleles have been complemented to the positive strand.
Article: Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement
Gene: CYP1A2
Variant/haplotype: rs2069514
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype GG are associated with decreased dose of warfarin in people with heart valve replacement as compared to genotype AA.
Article: A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics
Gene: HDAC1
Variant/haplotype: rs1741981
Drug(s): corticosteroids
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to corticosteroids in children with Asthma as compared to genotypes CT + TT.
Notes: Children with the CC genotype showed significantly lower percent forced expiratory volume in 1 second (%FEV1) increases in response to inhaled corticosteroids, as compared to those with the CT or TT genotype. Patients were treated for 8 weeks. Note that this allele was significantly related to asthma severity (same direction of association; corrected p=0.036).
Article: Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?
Gene: ABCC1
Variant/haplotype: rs3784864
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype AA.
Notes: ABCC1 rs3784864 G carrier is associated with increased risk of non-response to methotrexate.
Article: Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine
Gene: ADRB2
Variant/haplotype: rs1042713
Drug(s): dexmedetomidine
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with increased response to dexmedetomidine in people with surgery as compared to genotypes AG + GG.
Notes: as measured by shorter onset time. "In our study, homozygosity for the A allele (AA) was more quickly to arrive at the desired sedation status than carriers of the G allele (AG/GG) (18.55 ± 7.65 vs. 24.63 ± 18.94, p = 0.031). This means that homozygosity for the major allele A) of ADRB2 rs1042713 was associated with a higher susceptibility to DXM’s efficacy."
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Variant/haplotype: rs1835740
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 T.
Notes: No significant difference in allele frequency between responders and non-responders. Please note that alleles have been complemented to the positive strand.
Article: Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE Study
Gene: SV2C
Variant/haplotype: rs2134227
Drug(s): quetiapine
Phenotype category: Efficacy
Significant: no
Association: Genotype GG is not associated with response to quetiapine in people with Schizophrenia as compared to genotypes CC + CG.
Notes: Not significant after correction for multiple testing using the False Discovery Rate. Response was assessed by change in the total Positive and Negative Syndrome Scale (PANSS) score.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: MIA3
Variant/haplotype: rs3008610
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with trough concentration of vancomycin as compared to allele G.
Notes: The SNP was not associated with trough levels of vancomycin (first vancomycin trough documented in EMR after at least 3 doses vancomycin). Elimination constants were also calculated.
Article: Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study
Variant/haplotype: rs12749274
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to naltrexone in people with Alcoholism as compared to allele G.
Notes: The A allele was associated with an increased risk of relapse to heavy drinking in patients undergoing naltrexone treatment.
Article: A novel mutant variant of the CYP2D6 gene (CYP2D6 17) common in a black African population: association with diminished debrisoquine hydroxylase activity
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*17
Drug(s): debrisoquine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *17/*17 is associated with decreased metabolism of debrisoquine in healthy individuals as compared to CYP2D6 *1/*1 + *1/*2 + *1/*17.
Notes: MR of was higher for *17/*17 (n=10) mean value 3.94 as compared to *1/*17 (n=23) mean value 1.45 (p<0.001) or compared to mean MR values *1/*1(n=12) =0.56 or *1/*2 (n=13)=0.59 (both p<0.001).
Article: Impact of IL28B, APOH and ITPA Polymorphisms on Efficacy and Safety of TVR- or BOC-Based Triple Therapy in Treatment-Experienced HCV-1 Patients with Compensated Cirrhosis from the ANRS CO20-CUPIC Study
Gene: APOH
Variant/haplotype: rs8178822
Drug(s): boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, telaprevir
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with increased response to boceprevir, peginterferon alfa-2a, peginterferon alfa-2b, ribavirin or telaprevir in people with Hepatitis C, Chronic as compared to allele T.
Notes: This variant was not significantly associated with SVR to triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1.
Article: Enantiospecific Pharmacogenomics of Fluvastatin
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): fluvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with increased concentrations of fluvastatin in healthy individuals as compared to allele T.
Notes: This variant is significantly associated with increased area under the plasma concentration-time curve (AUC) of 3R,5S-fluvastatin and total fluvastatin (but not 3S,5R-fluvastatin) in the candidate gene study.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: NR1I2
Variant/haplotype: rs3814057
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 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 SNP for rs2276707.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: CALU
Variant/haplotype: rs2290228
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele G is not associated with dose of warfarin in people with heart valve replacement as compared to allele A.
Notes: Samples, genotypes and INRs from a cohort of 551 patients were used to derive an algorithm which was used to predict daily warfarin maintenance dose in a second cohort of 236 patients. Note: the authors state that "SNPs were tested for deviations from HWE using the chi-squared test, and for their association with the warfarin dose by Spearman correlation analysis using a *co-dominant* model."
Article: Replication study of polymorphisms associated with response to methotrexate in patients with rheumatoid arthritis
Variant/haplotype: rs4982133
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C.
Article: Association of Polymorphisms of the Mu Opioid Receptor Gene with the Severity of HIV Infection and Response to HIV Treatment
Gene: OPRM1
Variant/haplotype: rs671531
Drug(s): highly active antiretroviral therapy (haart)
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to highly active antiretroviral therapy (haart) in people with HIV Infections as compared to genotypes AA + AG.
Notes: Patients with the GG genotype showed no decrease in viral load following the initiation of HAART, while patients with the AA or AG genotypes had a decrease in viral load. This association was only found in Hispanic patients.
Article: The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of warfarin in children as compared to genotype CC.
Notes: Patients with the TT genotype required 48% the dose of those with the CC genotype. VKORC1 genotype was found to account for 13% of the variability in stable warfarin dose (mg/day). Please note that alleles have been complemented to the plus chromosomal strand.
Article: Cytochrome P4502D6 genotype does not determine response to clozapine
Gene: CYP2D6
Variant/haplotype: CYP2D6*1
Drug(s): clozapine
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 *1 is not associated with metabolism of clozapine in people with Schizophrenia.
Notes: CYP2D6 genotype was not associated with clozapine metabolism.
Article: Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population
Gene: SLC15A2
Variant/haplotype: rs1143672
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotype AA is associated with decreased dose of warfarin as compared to genotype GG.
Article: Enantiospecific Pharmacogenomics of Fluvastatin
Gene: SLCO1B1
Variant/haplotype: rs58310495
Drug(s): fluvastatin
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with increased concentrations of fluvastatin in healthy individuals as compared to allele C.
Notes: This variant is significantly associated with increased area under the plasma concentration-time curve (AUC) of 3R,5S-fluvastatin, but not 3S,5R-fluvastatin. The AUC was 34% larger per copy of the variant allele. This variant is strongly linked with SLCO1B1 c.521T>C (r2=0.69).
Article: Impact of CYP2C9, VKORC1 and CYP4F2 genetic polymorphisms on maintenance warfarin dosage in Han-Chinese patients: A systematic review and meta-analysis
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: Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients
Gene: CES1
Variant/haplotype: rs2307240
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT are associated with increased response to clopidogrel in people with Acute coronary syndrome as compared to genotype CC.
Notes: The authors investigated the association between genotypes and several clinical outcomes in patients with acute coronary syndrome who were also taking clopidogrel
Article: SLCO1B1 521T→C functional genetic polymorphism and lipid-lowering efficacy of multiple-dose pravastatin in Chinese coronary heart disease patients
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): pravastatin
Phenotype category: Efficacy
Significant: yes
Association: Genotype CT is associated with decreased response to pravastatin in people with Coronary Stenosis as compared to genotype TT.
Notes: as determined by a smaller reduction in total cholesterol in patients with the CT genotype compared to the TT genotype. Changes in LDL-C, HDL-C and triglycerides were not significantly different.
Article: Pharmacogenetics of opioid medications for relief of labor pain and post-cesarean pain: a systematic review and meta-analysis
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): opioids
Phenotype category: Dosage
Significant: yes
Association: Genotype GG is associated with increased dose of opioids in women with Caesarian section and Pain as compared to genotypes AA + AG.
Notes: "A significant difference was observed among carriers of rs1799971 GG genotype in comparison to carriers of the A-allele in terms of opioid dose requirement for pain management of post-cesarean pain (SMD: 0.59; 95% CI: 0.17–1.02; P = 0.006, Fig. 3B)." "Six studies including patients with post-cesarean pain only [18,19,20, 23, 37, 42] were available for the association between the recessive model of OPRM1 rs1799971 and total opioid consumption (Fig. 3B). "
Article: Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study
Gene: GLA
Variant/haplotype: rs727504348
Drug(s): migalastat
Phenotype category: Efficacy
Significant: not stated
Association: Allele T is associated with increased response to migalastat in people with Fabry Disease.
Notes: Patients carrying the T allele showed improvements in renal function, cardiac geometry (specifically, reductions in left ventricular mass index) and gastrointestinal symptoms as well as reductions in GL-3 inclusions and plasma lyso-Gb3 and an increase in PBMC alpha-Gal A activity when treated with migalastat. Clinical benefit of migalastat was not substantially affected by disease severity. This variant was designated as an 'amenable variant' to migalastat treatment following an in vitro assay where migalastat increased the activity of alpha-Gal A by at least 3%. As all data were derived from post hoc analysis, statistical analyses were not carried out. Variant referred to as Gly373Ser in the paper.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: ABCC2
Variant/haplotype: rs2273697
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.
Article: Gender‐specific association between preproendothelin‐1 genotype and reduction of systolic blood pressure during antihypertensive treatment‐‐‐results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA)
Gene: EDN1
Variant/haplotype: rs5370
Drug(s): atenolol, irbesartan
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GT + TT are not associated with response to atenolol and irbesartan in women with Essential hypertension as compared to genotype GG.
Notes: No significant difference in the change in systolic blood pressure (SBP) or diastolic blood pressure (DBP) between genotypes was seen, between baseline and 12 weeks. p-value was adjusted for age, dose, and SBP, DBP and left ventricular mass index (LVMI) at baseline.
Article: Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*3
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: no
Association: CYP2C9 *1/*3 + *3/*3 is not associated with resistance to clopidogrel in people with Stroke as compared to CYP2C9 *1/*1.
Article: The Relation Between CYP2C19 Genotype and Phenotype in Stented Patients on Maintenance Dual Antiplatelet Therapy
Gene: CYP2C19
Variant/haplotype: rs4244285
Drug(s): aspirin
Phenotype category: Efficacy
Significant: not stated
Association: Allele A is not associated with decreased response to aspirin in people with Coronary Artery Disease as compared to allele G.
Notes: Aspirin 81-325 mg/d for at least 2 weeks.  ADP-induced ex vivo platelet aggregation was measured.  *2 SNP.  Comparison was between A carriers and non-carriers.  [stat_test: chi-square]
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs768416963
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele T is associated with decreased metabolism of nicotine as compared to allele C.
Notes: Assigned as loss-of-function following in vitro assessments, in vivo associations and variant construct functional assignments.