shlokn/autogkb huggingface dataset:
Article: No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA
Gene: SLC6A2
Variant/haplotype: rs36029
Drug(s): 3,4-methylenedioxymethamphetamine
Phenotype category: Other
Significant: yes
Association: Genotype AA is associated with increased response to 3,4-methylenedioxymethamphetamine as compared to genotypes AG + GG.
Notes: The AA genotype was associated with increased mean arterial pressure, but not plasma concentrations , or heart rate.
Article: Gemcitabine Metabolic and Transporter Gene Polymorphisms Are Associated with Drug Toxicity and Efficacy in Patients with Locally Advanced Pancreatic Cancer
Gene: SLC28A1
Variant/haplotype: rs8187758
Drug(s): gemcitabine
Phenotype category: Efficacy, Toxicity
Significant: no
Association: Genotype CC is not associated with increased response to gemcitabine in people with Pancreatic Neoplasms as compared to genotypes AA + AC.
Notes: Tumor response to therapy, progression free survival, and risk of neutropenia development did not significantly differ between genotype groups.
Article: Naltrexone Modification of Drinking Effects in a Sub-Acute Treatment and Bar-Lab Paradigm: Influence of OPRM1 and Dopamine Transporter (SCL6A3) Genes
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): ethanol
Phenotype category: Efficacy, Toxicity
Significant: no
Association: Allele A is not associated with response to ethanol in people with Alcoholism as compared to allele G.
Notes: Authors caution that the lack of observed association between rs1799971 and alcohol consumption may be due to differences in the study cohort, bias or a type II error.
Article: SLC6A4 Variation and Citalopram Response
Gene: SLC6A4
Variant/haplotype: rs25531
Drug(s): citalopram
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to citalopram in people with Depression as compared to allele T.
Article: Effect of CYP4F2 Polymorphisms on Ticagrelor Pharmacokinetics in Healthy Chinese Volunteers
Gene: SLCO1B1
Variant/haplotype: rs4149032
Drug(s): AR-C124910XX, ticagrelor
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes CT + TT is not associated with decreased concentrations of AR-C124910XX or ticagrelor in healthy individuals as compared to genotype CC.
Notes: from TABLE 4 Ticagrelor pharmacokinetic parameters based on genotypes without statistical significance and TABLE 5; AR-C124910XX pharmacokinetic parameters based on genotypes without statistical significance
Article: Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder
Gene: ADH1C
Variant/haplotype: rs698
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to naltrexone in men with Alcoholism as compared to allele T.
Notes: Please note that alleles have been complemented to the positive strand. The C allele is also referred to as the ADH1C*1 allele in the paper. Patients carrying the C allele reported fewer drinking days during naltrexone treatment.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: GABRA3
Variant/haplotype: rs2201169
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele G 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. Please note that alleles have been complemented to the positive strand.
Article: A Delta-Opioid Receptor Gene Polymorphism Moderates the Therapeutic Response to Extended-Release Buprenorphine in Opioid Use Disorder
Gene: OPRD1
Variant/haplotype: rs678849
Drug(s): buprenorphine
Phenotype category: Efficacy
Significant: no
Association: Genotype CC is associated with increased response to buprenorphine in people with Opioid-Related Disorders as compared to genotypes CT + TT.
Notes: This was found in African Americans only. The opposite association was found in European Americans.
Article: Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizers and intermediate metabolizers
Drug(s): tramadol
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 intermediate metabolizer and poor metabolizer are associated with increased concentrations of tramadol in healthy individuals as compared to CYP2D6 normal metabolizer.
Notes: Note that no statistical analysis was carried out on data from the clinical study. All IMs had the *10/*10 genotype, while all PMs had the *5/*5 genotype. The genotypes of all NMs are not given and the study did not look for CNVs to identify UMs.
Article: Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR
Gene: CFTR
Variant/haplotype: rs113993960
Drug(s): ivacaftor, lumacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotype del/del is associated with response to ivacaftor and lumacaftor in people with Cystic Fibrosis.
Notes: Changes in FEV1, BMI, CFQ-R score and number of pulmonary exacerbation events were measured to determine response.
Article: Genetic variants in the KIF6 region and coronary event reduction from statin therapy
Gene: KIF6
Variant/haplotype: rs9471077
Drug(s): atorvastatin, pravastatin
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with increased response to atorvastatin or pravastatin.
Article: Assessing the Contribution of Opioid- and Dopamine-Related Genetic Polymorphisms to the Abuse Liability of Oxycodone
Gene: OPRD1
Variant/haplotype: rs10753331
Drug(s): oxycodone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to oxycodone as compared to allele G.
Notes: No association between this variant and analgesic response to oxycodone, as assessed by cold pressor test, subjective effects of oxycodone.
Article: Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation
Gene: CYP2B6
Variant/haplotype: rs3745274
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotypes GT + TT are associated with increased concentrations of efavirenz in children with HIV Infections as compared to genotype GG.
Article: Germline Variation in Colorectal Risk Loci Does Not Influence Treatment Effect or Survival in Metastatic Colorectal Cancer
Variant/haplotype: rs10795668
Drug(s): fluorouracil, irinotecan, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to fluorouracil, irinotecan and oxaliplatin in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to allele G.
Notes: SNPs were investigated for their effects on response rate, time to progression and overall survival. After accounting for multiple testing there was no association with any SNPs and outcomes of patients with metastatic colorectal cancer.
Article: Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis
Gene: TNFRSF1A
Variant/haplotype: rs767455
Drug(s): etanercept
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is not associated with response to etanercept in people with Spondylitis, Ankylosing as compared to genotypes CC + TT.
Notes: Response to etanercept was determined using the Assessment in Ankylosing Spondylitis 20 (ASAS20) and Assessment in Ankylosing Spondylitis 40 (ASAS40). No significant difference in response was seen between genotypes at either 3 months or 12 months after initiation of etanercept treatment.
Article: Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole
Gene: SLCO1B1
Variant/haplotype: SLCO1B1*1, SLCO1B1*5
Drug(s): estrone
Phenotype category: Efficacy
Significant: yes
Association: SLCO1B1 *5/*5 is associated with increased concentrations of estrone in women with Breast Neoplasms as compared to SLCO1B1 *1/*1 + *1/*5.
Notes: when treated with aromatase inhibitors.
Article: Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele A.
Notes: No significant difference in genotype or phenotype frequencies between responders and non-responders, as defined by drug misuse during methadone maintenance therapy. No details about which specific variants/alleles were tested for. Variant referred to as C3435T. Please note that alleles have been complemented to the positive strand.
Article: Identification of Cytochrome P450 Polymorphisms in Burn Patients and Impact on Fentanyl Pharmacokinetics: A Pilot Study
Gene: CYP3A4
Variant/haplotype: rs2740574
Drug(s): fentanyl
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele C is associated with decreased clearance of fentanyl in people with Burns as compared to allele T.
Notes: Single patient identified with the CYP3A4*1B allele. Clearance of fentanyl in this patient was significantly lower than in patients without the *1B allele. Mapped *1B to rs2740574 C and *1A to rs2740574 T based on PharmVAR consolidation of core alleles.
Article: Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): sunitinib
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased response to sunitinib in people with Carcinoma, Renal Cell.
Notes: The genotype was not associated with progression free survival, or overall survival. Clinical benefit is defined as either partial response or stable disease and lack of clinical benefit as progressive disease. This was more significant when calculated for the haplotype rs1045642 T, rs1128503 T, and rs2032582 T. Please note, alleles have been complemented to the + chromosomal strand.
Article: Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*8, CYP2C19*17
Drug(s): clopidogrel
Phenotype category: Efficacy, Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*2 + *1/*8 + *2/*2 (assigned as poor metabolizer phenotype) is associated with decreased response to clopidogrel in people with Coronary Artery Disease as compared to CYP2C19 *1/*1 + *1/*17 + *17/*17 (assigned as normal metabolizer phenotype) .
Notes: VASP platelet reactivity index and VerifyNow(TM) P2Y12 reaction unit values were significantly higher in PM than in EM.  Patients were also treated with aspirin.   There were 37 EM (by genotype) and 9 PM (by genotype).  Dosage was 600 mg loading/75 mg maintenance.
Article: Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 *1/*4 + *2/*4 + *1/*5 + *1/*3 + *2/*5 + *1/*6 + *2/*3 + *2/*6 are associated with decreased concentrations of endoxifen in women with Breast Neoplasms as compared to CYP2D6 *1/*2 + *1/*1 + *2/*2.
Notes: Pre- and post menopausal patients received 20 mg/day tamoxifen for at least 1 month (median duration 21.5 month). DNA source was blood and CYP2D6 was genotyped with TaqMan allelic discrimination assays. PM (non-functional) alleles include: CYP2D6*3, *4, *5, *6, *7; IM (reduced function) alleles include: CYP2D6*9, *10, *17, *41; EM (wt; fully functional) alleles include CYP2D6*1 and *2; UM (increased function) alleles include: duplication of EM variants of the gene, such as CYP2D6*1XN and *2XN. Patients were assigned a CYP2D6 genotype depending on the combination of alleles they carry, as PM/PM, IM/PM, IM/IM, EM/PM, EM/IM, EM/EM or EM/UM.
Article: Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants
Gene: CYP2D6
Variant/haplotype: CYP2D6*1, CYP2D6*4
Drug(s): amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline, opipramol
Phenotype category: Dosage, Efficacy
Significant: yes
Association: CYP2D6 *4/*4 is associated with decreased dose of amitriptyline, clomipramine, doxepin, imipramine, maprotiline, nortriptyline or Opipramol in people with Depression as compared to CYP2D6 *1/*1.
Notes: (*4*4 vs. *1*1; this SNP was the only SNP assayed and this method could not detect *5.) Tricyclic antidepressants were grouped together for this analysis (45.9 % of patients were taking Amitriptyline; 8.2% Maprotiline;6.6% Clomipramine; 2.9% Nortriptyline;2.4% Imipramine;0.7% Dosulepin;0.3% Doxepin;0.2% Opipramol.  Mean TCA dose was significantly lower at the 3rd and 4th prescription (difference 0.11 DDD). Genotypes were not in Hardy-Weinberg equilibrium; frequency below is for a larger population that included patients treated with other antidepressants.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: CYP2C9
Variant/haplotype: rs4917639
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele C is associated with decreased 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." rs4917639 only remained significantly associated with warfarin maintenance dose in the first cohort but did not remain significant in the multivariate analysis.
Article: Gene Variations of Sixth Complement Component Affecting Tacrolimus Metabolism in Patients with Liver Transplantation for Hepatocellular Carcinoma
Gene: C6
Variant/haplotype: rs7443562
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with dose-adjusted trough concentrations of tacrolimus in people with liver transplantation as compared to genotypes AG + GG.
Notes: No significant difference was seen when considering DONOR genotype at week 2 of treatment. Patients with hepatocellular carcinoma.
Article: A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*8
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *2 + *3 + *8 are associated with decreased dose of warfarin as compared to CYP2C9 *1.
Notes: The authors aimed to develop an admixture-adjusted (genetic ancestry) PGx dosing algorithm for warfarin in Caribbean Hispanics from Puerto Rico. [Algorithm R sq.=0.70, MAE = 0.72 mg/day]. When externally validated with 55 individuals from an independent cohort the novel algorithm predicted 58% of the warfarin dose variance [MAE = 0.89 mg/day, 24% mean bias]. Please note: the derivation cohort was 99% male and  "variables were included in final lin. reg model if p<0.05 or if association with daily warfarin dose was marginally significant 0.05 = p = 0.20 with strong biological plausibility".
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: rs4149056
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype CC is associated with decreased response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CT + TT.
Notes: Evidence of minimal residual disease at 78 days was higher in CC genotype vs. CT + TT.
Article: Effects of genetic polymorphisms on methotrexate levels and toxicity in Chinese patients with acute lymphoblastic leukemia
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased exposure to methotrexate in people with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotypes CC + CT.
Notes: increased concentrations at 48 and 72 hours which was also reported as "MTX elimination delay".  "MTX elimination delay was defined as MTX concentration of >1.0 μmol/L at 48 hours and >0.3 μmol/L at 72 hours." Authors report: "Moreover, MTX elimination delay was less in patients with SLC19A1 rs4149056 TC or CC genotype (OR 0.319, 95% CI: 0.138–0.736, P = 0.007)." this gives the wrong gene for this variant identifier.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: PPARA
Variant/haplotype: rs4253730
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 for rs4823613 and rs4253728.
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: CHRNA5
Variant/haplotype: rs621849
Drug(s): nicotine
Phenotype category: Other
Significant: no
Association: Allele G is not associated with exposure to nicotine in men as compared to allele A.
Notes: The G allele was initially associated with an increased likelihood of being a smoker but this lost significance following correction for multiple testing.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: CALCA
Variant/haplotype: rs3781719
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to botulinum toxin type a in women with Migraine NOS as compared to allele A.
Notes: The G allele was found at a significantly higher frequency in non-responders than in responders. Please note that alleles have been complemented to the positive strand.
Article: Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients
Gene: EPHX1
Variant/haplotype: rs1051740
Drug(s): carbamazepine
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with resistance to carbamazepine in people with Epilepsy as compared to genotypes CC + CT.
Notes: The authors evaluated the distribution of genotypes between individuals who developed resistance to carbamazepine (CBZ) and those who did not. There were no significant differences in genotype distributions between the two groups.
Article: COMT Val108/158Met polymorphism modulates task-oriented behaviour in children with ADHD
Gene: COMT
Variant/haplotype: rs4680
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 A.
Notes: No significant genotype by treatment interaction was observed (p=0.4), suggesting that COMT genotype does not modulate therapeutic response, at least at the dose of MPH tested (0.5¿mg/kg). Restricted Academic Situation Scale (RASS) was used.
Article: Polymorphic Variants of SCN1A and EPHX1 Influence Plasma Carbamazepine Concentration, Metabolism and Pharmacoresistance in a Population of Kosovar Albanian Epileptic Patients
Gene: SCN1A
Variant/haplotype: rs3812718
Drug(s): carbamazepine
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with increased metabolism of carbamazepine in people with Epilepsy as compared to genotypes CC + CT.
Notes: The authors evaluated maintenance dose-adjusted concentrations of carbamazepine (CBZ), its active metabolite, CBZ-epoxide (CBZE), and its inactive metabolite CBZ-diol (CBZD) as well as CBZE:CBZ, CBZD:CBZ and CBZD:CBZE ratios. The TT genotype is associated with a lower mean dose adj. concentration of CBZ (microgram/mL per mg/Kg) (0.71 for the TT genotype vs. 0.92-1.11 for the CT and CC genotypes, respectively) as well as a higher mean CBZD:CBZ (0.43 for TT vs. 0.23-0.27 for the CT and CC genotypes, respectively). Please note: alleles have been complemented to the + chromosomal strand.
Article: CALCA and TRPV1 genes polymorphisms are related to a good outcome in female chronic migraine patients treated with OnabotulinumtoxinA
Gene: TRPV3
Variant/haplotype: rs7217270
Drug(s): botulinum toxin type a
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to botulinum toxin type a in women with Migraine NOS as compared to allele G.
Notes: No significant difference in allele frequency between responders and non-responders.
Article: Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia
Gene: TPMT
Variant/haplotype: TPMT deficiency
Drug(s): deoxy-thioguanosine triphosphate, thioguanosine triphosphate
Phenotype category: Metabolism/PK
Significant: not stated
Association: TPMT deficiency is associated with increased concentrations of deoxy-thioguanosine triphosphate and thioguanosine triphosphate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma.
Notes: These two children had higher levels of intracellular 6-thioguanine nucleotides, while taking 25% of the standard protocol dose, than did  the other patients who were taking 100% of the protocol dose.
Article: Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril
Gene: CES1
Variant/haplotype: rs71647871
Drug(s): quinapril
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype CT is not associated with clearance of quinapril in healthy individuals as compared to genotype CC.
Notes: This was a fixed-order crossover study with two phases: following overnight fasting participants took a 10 mg dose of quinapril and, after a washout period of at least 1 week, a 10 mg dose of enalapril with 150 ml water in the morning and EDTA-prepared blood samples were drawn before and up to 24 hr, and up to 48 h after ingestion for the determination of the concentrations of quinapril and its metabolite quinaprilat, as well as enalapril and its metabolite enalaprilat. Urine was collected up to 12 h after quinapril and enalapril. Only AUC (0-infinity) and amount excreted in urine of enalaprilat were significantly different between genotype groups. Other PK parameters that were tested and not significantly different were Cmax, Tmax, T(1/2), and renal clearance.