shlokn/autogkb huggingface dataset:
Article: Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with increased metabolism of tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: CYP3A5*1 carriers showed 2-3 fold lower C0/dose and C2/dose of tacrolimus compared to CYP3A5*3 homozygotes.  Population pharmacokinetics modelling using both univariate and multivariate analysis, CYP3A5*1 allele was the significant covariate for pharmacokinetics parameter CL/F.
Article: Genetic-based dosing in orthopedic patients beginning warfarin therapy
Gene: CYP2C9
Variant/haplotype: rs1799853
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin in people with total knee or hip arthroplasty as compared to allele C.
Notes: T (*2) was associated with 17.4 %(95% CI 8.3-25.6%) reduction in therapeutic dose (defined as the dose that gave an INR in the target therapeutic range after 7 consecutive days) per copy.
Article: Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes
Gene: ABCC8, KCNJ11
Variant/haplotype: rs5219
Drug(s): "metformin", "sulfonamides, urea derivatives"
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CT + TT is associated with increased clinical benefit to metformin and sulfonamides, urea derivatives in people with Diabetes Mellitus, Type 2 as compared to genotype CC.
Notes: "Relative to the rs5219 EE genotype carriers, the EK and KK genotype carriers responded better to combination therapy." However Table 4 shows E as higher frequency in responders than non-responders.  Mapped E to C and K to T.
Article: Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes CT + TT is associated with increased clearance of tacrolimus in people with Kidney Transplantation as compared to genotype CC.
Notes: Patients who were CYP3A5 expressors (CT + TT) had 30% (95% CI = 13, 46%) higher tacrolimus clearance, and 18% (95% CI = 2, 29%) lower tacrolimus bioavailability, as compared to nonexpressors (CC).
Article: Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians
Gene: CYP4F2
Variant/haplotype: rs2108622
Drug(s): acenocoumarol
Phenotype category: Dosage
Significant: no
Association: Genotype CC is not associated with decreased dose of acenocoumarol as compared to genotypes CT + TT.
Notes: No significant difference was seen between the daily dose for CYP4F2 wildtype patients and the daily dose for CYP4F2 variant carriers. This study provides an algorithm for predicting the maintenance dose of acenocoumarol using genotypes as well as clinical factors as predictive variables.
Article: Effect of eNOS polymorphisms on salbutamol evoked endothelium dependent vasodilation in South Indian healthy subjects
Gene: NOS3
Variant/haplotype: rs2070744
Drug(s): salbutamol
Phenotype category: Efficacy
Significant: no
Association: Genotype TT is not associated with response to salbutamol in healthy individuals as compared to genotypes CC + CT.
Notes: No significant differences in the change in digital volume pulse parameters - reflection index and stiffness index - before and after salbutamol administration were seen between the two genotype groups. This indicates that this SNP does not affect salbutamol-evoked endothelium-dependent vasodilation.
Article: Variant‐based heritability assessment of dexmedetomidine and fentanyl clearance in pediatric patients
Gene: CPPED1
Variant/haplotype: rs111860321
Drug(s): fentanyl
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is associated with decreased clearance of fentanyl in children with Pain, Postoperative as compared to allele T.
Notes: Data from Table S3, direction of effect and risk allele not clear. Minor allele and frequency stated. Mapped to dbSNP using genomic location 16:12920566:C:T on hg19/GRCh37. "GWAS failed to identify any variants meeting the genome-wide statistical significance threshold of 5 × 10−8" This is top scoring variant.
Article: CYP2B6*6 Genotype Specific Differences in Artemether‐Lumefantrine Disposition in Healthy Volunteers
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*6
Drug(s): lumefantrine
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2B6 *6/*6 is not associated with metabolism of lumefantrine in healthy individuals as compared to CYP2B6 *1/*1.
Notes: No significant difference in in metabolic ratio or any other PK parameters assessed between the genotype groups.
Article: Response to the dipeptidyl peptidase-4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin-6 promoter region under a certain level of physical activity
Gene: IL6
Variant/haplotype: rs1800796
Drug(s): alogliptin, linagliptin, sitagliptin, teneligliptin, vildagliptin
Phenotype category: Efficacy
Significant: no
Association: Allele G is associated with increased response to alogliptin, linagliptin, sitagliptin, teneligliptin or vildagliptin in people with Diabetes Mellitus, Type 2 as compared to allele C.
Notes: "The result showed that the diplotype rs1800796 G/*–rs2097677 A/* had a lower risk for being non-responders than C/C-G/G in the moderate/high group (adjusted odds ratio 0.153, 95% CI 0.044–0.535, P = 0.003), but not in the low group (Table6)."
Article: Functional genetic variation in the Rev-Erbα pathway and lithium response in the treatment of bipolar disorder
Gene: BMAL1
Variant/haplotype: rs2279287
Drug(s): lithium
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with increased response to lithium in people with Bipolar Disorder as compared to allele C.
Article: KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
Gene: KLB
Variant/haplotype: rs11940694
Drug(s): ethanol
Phenotype category: Toxicity
Significant: yes
Association: Allele A is associated with decreased dose of ethanol as compared to allele G.
Notes: A GWAS of variants associated with alcohol drinking found that the A allele was associated with reduced levels of drinking.
Article: Association of Regulatory Genetic Variants for Protein Kinase C α with Mortality and Drug Efficacy in Patients with Heart Failure
Gene: PRKCA
Variant/haplotype: rs9303504
Drug(s): "Ace Inhibitors, Plain", "Angiotensin II Antagonists", "Beta Blocking Agents"
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to Ace Inhibitors, Plain, Angiotensin II Antagonists or Beta Blocking Agents in people with Heart Failure as compared to allele C.
Notes: The authors note that this variant was in strong LD with rs9909004.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: CALU
Variant/haplotype: rs339097
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: Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial
Gene: HTR2A
Variant/haplotype: rs7997012
Drug(s): escitalopram
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to escitalopram in people with Depression as compared to allele G.
Article: IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection
Gene: IFNL3
Variant/haplotype: rs7248668
Drug(s): peginterferon alfa-2b, ribavirin
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG is associated with decreased response to peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic as compared to genotype GG.
Notes: This genotype has decreased association with sustained virological response (SVR).
Article: A published pharmacogenetic algorithm was poorly predictive of tacrolimus clearance in an independent cohort of renal transplant recipients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*1 is associated with increased clearance of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: Genotype *1/*1 vs *3/*3 was reported. Clearance was estimated using the dose-normalized whole-blood trough concentration. The DeKAF algorithm was tested but it failed to predict tacrolimus clearance in this cohort.
Article: Correlation of MDR1 gene polymorphism with propofol combined with remifentanil anesthesia in pediatric tonsillectomy
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): propofol, remifentanil
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to propofol and remifentanil in children as compared to allele A.
Notes: Referred to as 3435 C>T in the paper. Please note that alleles have been complemented to the positive strand.
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizer and intermediate metabolizer genotypes
Drug(s): tamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2D6 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of tamoxifen in women with Breast Neoplasms.
Article: Escitalopram and sertraline population pharmacokinetic analysis in pediatric patients
Gene: CYP2C19
Variant/haplotype: CYP2C19 rapid metabolizer
Drug(s): escitalopram
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 ultrarapid metabolizer and rapid metabolizer is associated with increased clearance of escitalopram in children as compared to CYP2C19 normal metabolizer.
Notes: "On average, poor and intermediate metabolizers had 69% and 20%; slower CL/F relative to normal metabolizers, respectively,; whereas rapid and ultrarapid metabolizers had 18% and; 23% faster CL/F, respectively"
Article: Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model
Gene: VKORC1
Variant/haplotype: rs7294
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT is associated with increased dose of warfarin in people with Cardiovascular Diseases as compared to genotype CC.
Notes: This SNP was presented as VKORC1 3730G>A. Patients carrying the T allele showed significantly higher doses of warfarin as compared to patients with the wildtype genotype, CC.
Article: TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population
Gene: TAOK3
Variant/haplotype: rs1277441
Drug(s): morphine
Phenotype category: Dosage, Efficacy
Significant: yes
Association: Genotype GG is associated with increased dose of morphine in children with Pain, Postoperative as compared to genotypes AA + AG.
Notes: Association described as 'nominally significant' in the paper and was only seen in European Caucasian patients. Please note that alleles have been complemented to the positive strand.
Article: The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients
Gene: SLC19A1
Variant/haplotype: rs1051266
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased clinical benefit to methotrexate in people with Arthritis, Rheumatoid as compared to genotypes CC + CT.
Notes: "This clarified that the 80 AA genotype of RFC1 G80A was linked to a better response to MTX treatment. Multivariate regression analysis confirmed this result. It showed that RFC1 (GA + GG) increased the risk of not responding to MTX by 3.838-fold." Alleles complemented to plus chromosomal strand.
Article: 5-HTR1A and 5-HTR2A genetic polymorphisms and SSRI antidepressant response in depressive Chinese patients
Gene: HTR2A
Variant/haplotype: rs6311
Drug(s): citalopram, fluoxetine, paroxetine, sertraline
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to citalopram, fluoxetine, paroxetine or sertraline in people with Depressive Disorder, Major as compared to allele C.
Notes: Response/remission measured using HAMD.
Article: ABCB1 Genotype is Associated with Fentanyl Requirements in Critically Ill Children
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): fentanyl
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to fentanyl in children as compared to genotypes AG + GG.
Notes: No significant difference in average FLACC score between genotype groups.
Article: CYP2D6 Genotyping as an alternative to phenotyping for determination of metabolic status in a clinical trial setting
Gene: CYP2D6
Variant/haplotype: CYP2D6*4, CYP2D6*15
Drug(s): debrisoquine, dextromethorphan
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP2D6 *4/*15 is associated with decreased metabolism of debrisoquine or dextromethorphan.
Notes: Out of 558 subjects previously phenotyped for clinical studies and genotyped for this study, 46 PM were found.  1 of these 46 was *4/*15.
Article: Effects of Opioid Receptor Gene Variation on Targeted Nalmefene Treatment in Heavy Drinkers
Gene: OPRK1
Variant/haplotype: rs963549
Drug(s): nalmefene
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to nalmefene in people with Alcoholism as compared to allele T.
Article: A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression
Gene: HTR7
Variant/haplotype: rs7905446
Drug(s): paroxetine
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with decreased response to paroxetine in people with Bipolar Disorder as compared to genotypes GG + GT.
Notes: A 'good' response was determined as a 50% reduction in symptoms or episode frequency during the course of the illness.
Article: Race influences warfarin dose changes associated with genetic factors
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Genotypes CT + TT are associated with decreased dose of warfarin as compared to genotype CC.
Notes: in both European Americans and African Americans. However, the dose reduction per variant allele was higher among European Americans (28.3% vs 18.6%, interaction P value=0.002) compared with African Americans.
Article: Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients
Gene: CYP3A5
Variant/haplotype: rs10264272
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. Unlike most of the CYP3A variants, this did not pass validation the authors speculate this is because of low frequency particularly in the AA cohort.
Article: The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study
Gene: ADRA2A
Variant/haplotype: rs1800545
Drug(s): dexmedetomidine
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of dexmedetomidine in men as compared to allele G.
Article: Gene‐Wide Tagging Study of the Association Between KCNT1 Polymorphisms and the Susceptibility and Efficacy of Genetic Generalized Epilepsy in Chinese Population
Gene: KCNT1
Variant/haplotype: rs10858173
Drug(s): antiepileptics
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to antiepileptics in people with Epilepsy, Generalized as compared to allele T.
Notes: No significant differences in genotype frequencies were seen between patients who were responsive to antiepileptic drugs (n=279; those who had not experienced any type of seizure for a minimum of 1 year after receiving antiepileptic drugs) and patients who were resistant to antiepileptic drugs (n=204; those who had at least four seizures during the previous year while trying at least three antiepileptic medications at the maximal tolerated doses).
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP3A4
Variant/haplotype: CYP3A4 poor metabolizer and intermediate metabolizer genotypes
Drug(s): 4-hydroxytamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A4 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of 4-hydroxytamoxifen in women with Breast Neoplasms.
Article: Effect of the Most Relevant CYP3A4 and CYP3A5 Polymorphisms on the Pharmacokinetic Parameters of 10 CYP3A Substrates
Gene: CYP3A4
Variant/haplotype: rs35599367
Drug(s): ambrisentan, aripiprazole, atorvastatin, donepezil, olanzapine
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with metabolism of ambrisentan, aripiprazole, atorvastatin, donepezil or olanzapine in healthy individuals as compared to allele G.
Notes: No significant changes in PK parameters in the presence of the A allele. The A allele is also referred to in the paper as the CYP3A4*22 allele.
Article: Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia
Gene: ABCB1
Variant/haplotype: rs2032582
Drug(s): doxorubicin, methotrexate, prednisolone, vincristine
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with resistance to doxorubicin, methotrexate, prednisolone and vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele C.
Notes: No statistically significant differences in relapse risk were found between the alleles or genotypes of rs2032582 G>A/T. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Pharmacogenetic analysis of belimumab fails to identify robust genetic predictors of efficacy in lupus
Gene: ANO3
Variant/haplotype: rs293983
Drug(s): belimumab
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to belimumab in people with Lupus erythematosus as compared to allele C.
Notes: Confirmatory analysis of the SRI4 end point in an independent phase 3 study of SLE patients from northeast Asia could not confirm evidence of an association between rs293983 and SRI4 response.
Article: Comprehensive Ara-C SNP score predicts leukemic cell intracellular ara-CTP levels in pediatric acute myeloid leukemia patients
Gene: CTPS1
Variant/haplotype: rs12067645
Drug(s): ara-CTP
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotypes AA + AG is associated with increased concentrations of ara-CTP in children with Leukemia, Myeloid, Acute as compared to genotype GG.
Article: Association of Genetic Variation in Cystathionine-β-Synthase and Arsenic Metabolism
Gene: CBS
Variant/haplotype: rs234709
Drug(s): Arsenic compounds
Phenotype category: Toxicity, Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with increased metabolism of Arsenic compounds as compared to genotype CC.
Notes: measured as as excreted monomethylarsonic acid.
Article: Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): sunitinib
Phenotype category: Efficacy
Significant: no
Association: Genotype AA is not associated with response to sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AG + GG.
Notes: The genotype was not associated with clinical benefit, progression free survival, or overall survival. However a haplotype containing this variant (haplotype rs1045642 T, rs1128503 T, and rs2032582 T) was significant. Clinical benefit was defined as either partial response or stable disease. Please note, alleles have been complemented to the + chromosomal strand.
Article: Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes
Gene: CYP2A6
Variant/haplotype: rs200554095
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: not stated
Association: Allele A is associated with decreased metabolism of nicotine as compared to allele T.
Notes: Assigned as loss-of-function following in vitro assessments, in vivo associations and variant construct functional assignments.
Article: Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial
Gene: OPRM1
Variant/haplotype: rs609148
Drug(s): naltrexone
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to naltrexone in people with Tobacco Use Disorder as compared to allele G.
Notes: No significant association between this variant and smoking quit rate when naltrexone was used as augmentation to nicotine patch therapy.
Article: IFNL4-ΔG Genotype Is Associated With Slower Viral Clearance in Hepatitis C, Genotype-1 Patients Treated With Sofosbuvir and Ribavirin
Gene: IFNL4
Variant/haplotype: rs11322783
Drug(s): ribavirin, sofosbuvir
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with decreased response to ribavirin and sofosbuvir in people with Hepatitis C, Chronic as compared to genotypes G/TT + TT/TT.
Notes: in hepatitis C, genotype-1 patients. Delta-G genotype is also associated with slower viral clearance in hepatitis C, genotype-1 patients treated with sofosbuvir and ribavirin.
Article: Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): levonorgestrel
Phenotype category: Metabolism/PK
Significant: no
Association: NAT2 slow acetylator is associated with decreased clearance of levonorgestrel in women with Tuberculosis as compared to NAT2 rapid acetylator.
Notes: Study investigated the effect on steady-state drugs used to treat HIV or tuberculosis on the pharmacokinetics of single dose levonorgestrel. Association found in the cohort treated with Isoniazid and rifampin.; Slow acetylators were defined as being homozygous for the NAT2*5, *6, *7 and/or *14 alleles or being heterozygous at at least 2 loci.