shlokn/autogkb huggingface dataset:
Article: Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians
Gene: SLCO1B1
Variant/haplotype: rs4149056
Drug(s): simvastatin acid
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype CT is associated with increased concentrations of simvastatin acid in healthy individuals as compared to genotype TT.
Article: Population pharmacokinetics of tacrolimus whole blood and peripheral blood mononuclear cell concentrations in stable kidney‐transplanted patients
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: not stated
Association: CYP3A5 *3/*3 is associated with increased concentrations of tacrolimus in people with Kidney Transplantation as compared to CYP3A5 *1/*1 + *1/*3.
Notes: "CYP3A5 non-expressors had a 46.6% lower CL/F than expressors(Table 2), which is in line with multiple previous models. Additionally, CYP3A5 non-expressors had a 42.4% higher RC:PBMC than expressors, so the difference in PBMC concentrations between an expressor and a non-expressor is even greater than the difference in wholeblood concentrations (Figure 5D)" RC:PBMC = ratio of tacrolimus whole blood to PBMCconcentration
Article: An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans
Gene: OPRD1
Variant/haplotype: rs678849
Drug(s): methadone
Phenotype category: Efficacy
Significant: no
Association: Allele C is not associated with response to methadone in people with Opioid-Related Disorders as compared to allele T.
Notes: Efficacy was determined based on the number of opioid-positive drug screens that each patient had during treatment.
Article: Using EHR-Linked Biobank Data to Study Metformin Pharmacogenomics
Gene: SLC22A3
Variant/haplotype: rs3127602
Drug(s): metformin
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with increased response to metformin in people with Diabetes Mellitus, Type 2 as compared to allele C.
Notes: Authors looked at candidate genes in patients that had previously had genome sequencing. They look quite far outside of conventional gene boundaries. "For each candidate gene we selected SNPs 50 kb upstream and downstream of each gene using 1000 genomes project variants and NCBI build 37 as the reference genome." Table 2 shows rs3127602 as top SNP for SLC22A3
Article: Influence of Cytochrome P450 2C19 Genotype on Helicobacter pylori Proton Pump Inhibitor-Amoxicillin-Clarithromycin Eradication Therapy: A Meta-Analysis
Gene: CYP2C19
Variant/haplotype: CYP2C19 normal metabolizer genotype
Drug(s): amoxicillin, clarithromycin, rabeprazole
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 normal metabolizer is not associated with decreased clinical benefit to amoxicillin, clarithromycin and rabeprazole in people with Helicobacter Infections as compared to CYP2C19 poor metabolizer.
Notes: "In contrast, studies that used rabeprazole and esomeprazole showed no significant differences in the RR of failed eradication among the three genotypes"
Article: Genetic factors influencing warfarin dose in Black-African patients: a systematic review and meta-analysis
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*6
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: CYP2C9 *1/*6 is associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: In this meta-analysis of warfarin Dose in Black-African Patients, CYP2C9*6 allele is associated with 8.1mg/week less warfarin dose requirement compared to wild-type homozygotes.
Article: Dual single‑nucleotide polymorphism biomarker combination for opioid selection to treat cancer pain
Gene: CCL11
Variant/haplotype: rs17809012
Drug(s): morphine
Phenotype category: Efficacy
Significant: yes
Association: Genotype AA is associated with decreased clinical benefit to morphine in people with Neoplasms and Pain as compared to genotypes AG + GG.
Notes: "Patients of Group M with the major CCL11 rs17809012 genotype (AA) showed a significantly reduced ∆NRS (P=0.006), suggesting that oxycodone should be preferred for patients with this genotype of CCL11 to obtain better pain relief. However, for the patients with the minor allele of the rs17809012 (AG/GG), morphine appeared to be a better choice, but this interaction was not statistically significant (P=0.358)."
Article: Novel Associations of VKORC1 Variants with Higher Acenocoumarol Requirements
Gene: VKORC1
Variant/haplotype: rs17878544
Drug(s): acenocoumarol
Phenotype category: Dosage
Significant: yes
Association: Genotype TT is associated with decreased dose of acenocoumarol as compared to genotypes CC + CT.
Notes: 14 vs 15 mg/week.
Article: Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?
Gene: SLC22A11
Variant/haplotype: rs11231809
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AT + TT are associated with decreased response to methotrexate in people with Arthritis, Rheumatoid as compared to genotype AA.
Notes: SLC22A11 rs11231809 T carrier is associated with increased risk of non-response to methotrexate.
Article: ANO2 Genetic Variants and Anti-VEGF Treatment Response in Neovascular AMD: A Pharmacogenetic Substudy of VIEW 1 and VIEW 2
Gene: ANO2
Variant/haplotype: rs2110166
Drug(s): aflibercept, ranibizumab
Phenotype category: Efficacy
Significant: yes
Association: Genotype TT is associated with increased clinical benefit to aflibercept or ranibizumab in people with Macular Degeneration as compared to genotypes CC + CT.
Notes: "In the pharmacogenetic study population, 50 patients had the rs2110166 TC genotype and 684 patients had the TT genotype; only one patient had the CC genotype." "Further regional plot analysis (Fig. 2) identified the ANO2 rs2110166 SNP as highly significantly associated with losing ≥5 ETDRS letters during anti-VEGF therapy in nAMD (P = 1.99 × 10–8)." "Carriers of the ANO2 rs2110166 TT genotype showed a robust increase in visual acuity versus baseline compared with a small decrease in those with the TC genotype."
Article: Effects of Opioid Receptor Gene Variation on Targeted Nalmefene Treatment in Heavy Drinkers
Gene: OPRD1
Variant/haplotype: rs678849
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: Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation
Gene: SLCO1B1
Variant/haplotype: rs2306283
Drug(s): mycophenolic acid
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is associated with decreased concentrations of mycophenolic acid in people with lung transplantation as compared to genotypes AG + GG.
Notes: Concentrations measured as trough blood drug concentrations.
Article: Pharmacogenetic Interactions of Rifapentine plus Isoniazid with Efavirenz or Nevirapine
Gene: NAT2
Variant/haplotype: NAT2 slow acetylator
Drug(s): rifapentine
Phenotype category: Metabolism/PK
Significant: not stated
Association: NAT2 slow acetylator is associated with increased concentrations of rifapentine in people with HIV Infections.
Notes: NAT2 slow acetylators had greater week 4 plasma concentrations of rifapentine (P = 2.6 × 10) and 25-desacetyl rifapentine (P = 7.0 × 10) among all participants, and in efavirenz and nevirapine subgroups.
Article: Population Pharmacokinetic Analysis and Pharmacogenetics of Raltegravir in HIV-Positive and Healthy Individuals
Gene: UGT1A9
Variant/haplotype: UGT1A9*3a
Drug(s): raltegravir
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A9 *3a is associated with increased exposure to raltegravir in people with HIV.
Notes: Out of ninety-six SNPs tested for their effect on bioavailability of raltegravir only rs72551330 (T>C) reached Bonferroni-corrected significance (set at 5.21 x 10^-4). The authors state that the effect of the SNP on raltegravir bioavailbility is mainly attributable to a single homozygous individual with very high raltegravir bioavialbility. The SNP could not be validated in a data set including 219 HIV positive patients and 19 healthy volunteers.
Article: Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry
Gene: NUDT15
Variant/haplotype: rs746071566
Drug(s): mercaptopurine
Phenotype category: Dosage, Toxicity
Significant: not stated
Association: Allele del is associated with decreased dose of mercaptopurine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele GGAGTC.
Notes: The variant was in 3 patients at St Jude's. One patient tolerated 43.5 mg/m2/day of mercaptopurine during the maintenance phase, The second patient was treated on the TOT XIIIB protocol, for which maintenance therapy consisted of drug pairs administered in weekly rotation and mercaptopurine given for only 1 week every 4-week period but did not experience significant toxicity and tolerated dosage was 82.5 mg/m2/day for that week.  In the 3rd patient, the variant was present along with rs116855232 C>T, and another variant with no rsID (K35E c.103A>G). Nucleotide diphosphotase activity could not be detected in in vitro studies.
Article: Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients
Gene: ATIC
Variant/haplotype: rs2372536
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methotrexate in people with Arthritis, Rheumatoid as compared to allele C.
Article: Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia
Gene: ABCC2
Variant/haplotype: rs3740065
Drug(s): methotrexate
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with clearance of methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele A.
Notes: All patients received four cycles of high dose MTX (5000mg per square meter of body surface area). 1/10th of the dose was administered over 30 minutes (rapid infusion) and the rest was administered continuously over 24hrs. Leucovorin rescue was administered every 6hrs starting 48 hrs after initiation of MTX infusion.
Article: Thymidylate Synthase Genotype-Directed Chemotherapy for Patients with Gastric and Gastroesophageal Junction Cancers
Gene: ERCC2
Variant/haplotype: rs13181
Drug(s): fluorouracil, leucovorin, oxaliplatin
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to fluorouracil, leucovorin and oxaliplatin in people with Esophageal Neoplasms and Stomach Neoplasms as compared to allele G.
Article: Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population
Gene: CYP2C18
Variant/haplotype: rs2860840
Drug(s): sertraline
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype TT is associated with decreased concentrations of sertraline as compared to genotype CC.
Notes: Compared with the reference group (CYP2C19*1/*1), a lower sertraline serum concentration was observed in CYP2C19*17/*17 (21.6% decrease, n = 44, p = 0.003), CYP2C:TG/CYP2C:TG (rs2860840 and rs11188059 together; 21.2% decrease, n = 26, p = 0.022), CYP2C19*17/ CYP2C:TG (20.0% decrease, n = 65, p = 0.003), and CYP2C19*1/*17 (17.0% decrease, n = 150, p < 0.001) patients, while no significant impact of CYP2C19*1/ CYP2C:TG genotype was detected in this patient population (n = 142, p > 0.1).
Article: VKORC1 and Novel CYP2C9 Variation Predict Warfarin Response in Alaska Native and American Indian People
Gene: CYP2C9
Variant/haplotype: CYP2C9*1, CYP2C9*2
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: CYP2C9 *2 is not associated with decreased dose of warfarin as compared to CYP2C9 *1/*1.
Notes: in Alaska Native and American Indian People.
Article: Genetic variants in CYP2B6 and CYP2A6 explain interindividual variation in efavirenz plasma concentrations of HIV-infected children with diverse ethnic origin
Gene: CYP2B6
Variant/haplotype: rs28399499
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Allele C is not associated with concentrations of efavirenz in children with HIV Infections as compared to allele T.
Notes: This is stated in the paper, but supporting data is not shown.; Allele also known as CYP2B6*18.
Article: An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3′-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients
Gene: NR1I2
Variant/haplotype: rs3814057
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: Genotype AA is not associated with concentrations of efavirenz in people with HIV Infections as compared to genotypes AC + CC.
Article: Relationship of CYP3A5 genotype and ABCB1 diplotype to tacrolimus disposition in Brazilian kidney transplant patients
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: Genotype AA is associated with decreased clearance of tacrolimus in people with Kidney Transplantation as compared to genotypes AG + GG.
Notes: 3 - 12 months post-transplant. In multivariate linear regression analysis, the AAA/AAA haplotype (rs1045642, rs1128503, rs2032582) showed a significant effect on dose-adjusted trough concentrations (C0/D) of tacrolimus (those with the AAA/AAA haplotype have increased C0/D compared to those with non-AAA/AAA haplotypes). In chi-squared analyses, no significant association was seen for trough concentrations or dose. Please note alleles have been complemented to the plus chromosomal strand.
Article: Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy
Gene: MIA3
Variant/haplotype: rs2088514
Drug(s): vancomycin
Phenotype category: Metabolism/PK
Significant: no
Association: Allele G is not associated with trough concentration of vancomycin as compared to allele A.
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: SNPs in PRKG1 and SPATA13-AS1 are associated with bronchodilator response: A pilot study during acute asthma exacerbations in African American children
Variant/haplotype: rs7903366
Drug(s): salbutamol
Phenotype category: Efficacy
Significant: yes
Association: Allele T is associated with decreased response to salbutamol in children with Asthma as compared to allele C.
Notes: rs7903366 was significantly negatively associated with having a high bronchodilator response category in an adjusted analysis. Risk allele not explicit stated in text only in table 1 summarizing prior studies.
Article: ST13 polymorphisms and their effect on exacerbations in steroid-treated asthmatic children and young adults
Gene: ST13
Variant/haplotype: rs138335
Drug(s): corticosteroids
Phenotype category: Efficacy
Significant: yes
Association: Allele G is associated with decreased response to corticosteroids in children with Asthma as compared to allele C.
Notes: Outcome measured was hospital visits for airway exacerbation. Effect is additive, measured per G allele.
Article: Population pharmacokinetic analysis of tacrolimus in Mexican paediatric renal transplant patients: role of CYP3A5 genotype and formulation
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): tacrolimus
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*1 + *1/*3 is associated with increased clearance of tacrolimus in children with Kidney Transplantation as compared to CYP3A5 *3/*3.
Notes: Population pharmacokinetic modeling. CYP3A5*1/*1 and *1/*3 carriers (CYP3A5 expressers) had approximately 2- and 1.5-fold higher clearance, respectively, as compared to CYP3A5*3/*3 carriers (CYP3A5 non-expressers). The authors also note that CYP3A5 genotype explained almost the entire inter-patient variability in clearance. Lastly, they note that individuals taking Limustin had significantly higher predicted doses of tacrolimus for all genotypes as compared to those taking Prograf (p<0.001).
Article: Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2
Gene: CHRNA3
Variant/haplotype: rs7170068
Drug(s): cotinine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele A is associated with increased concentrations of cotinine in people with Tobacco Use Disorder as compared to allele G.
Notes: The authors conducted a GWAS meta-analysis to identify genetic variants associated with cotinine in current daily smokers (Caucasian). The following study cohorts were analyzed: ALSPAC, CARDIA, FinnTwin, Framingham, GenMets, MESA, NESDA, NTR, TwinsUK, YFS. This SNP was detected as a residual association after accounting for rs16969968.
Article: TSPAN5, ERICH3 and selective serotonin reuptake inhibitors in major depressive disorder: pharmacometabolomics-informed pharmacogenomics
Gene: ERICH3
Variant/haplotype: rs11580409
Drug(s): antidepressants, citalopram, escitalopram
Phenotype category: Efficacy
Significant: yes
Association: Allele C is associated with increased response to antidepressants, citalopram and escitalopram in people with Depressive Disorder as compared to allele A.
Notes: This is one of SNP in a cluster (rs11580409 and rs11210490 and rs696692) that showed some association with plasma serotonin concentrations and was suspected to be associated with SSRI clinical response. Please note that the allele associated with clinical response was not specified in the paper. In a follow up paper (PMID: 33230203), the author stated that "the rs11580409 variant allele (C) was significantly associated with better response" and and demonstrated its association in another population of depressed patients (PReDICT) as well as its overall significance in a meta-analysis.
Article: Early Improvement and Marriage Are Determinants of the 12-Month Treatment Outcome of Paroxetine in Outpatients with Panic Disorder
Gene: SLC6A4
Variant/haplotype: SLC6A4 HTTLPR long form (L allele), SLC6A4 HTTLPR short form (S allele)
Drug(s): paroxetine
Phenotype category: Efficacy
Significant: no
Association: SLC6A4 HTTLPR long form (L allele) is not associated with response to paroxetine in people with Panic Disorder as compared to SLC6A4 HTTLPR short form (S allele).
Notes: The 5-HTTLPR was not associated with significant differences in early improvement in patients with panic disorder receiving paroxetine.
Article: CYP3A5 and ABCB1 genotype influence tacrolimus and sirolimus pharmacokinetics in renal transplant recipients
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): sirolimus, tacrolimus
Phenotype category: Metabolism/PK
Significant: no
Association: Allele A is not associated with metabolism of sirolimus or tacrolimus in people with Kidney Transplantation as compared to allele G.
Notes: No associations with tacrolimus or sirolimus pharmacokinetic parameters were seen for this SNP. Please note that alleles have been complemented to the plus chromosomal strand.
Article: Pharmacogenetics of warfarin in a paediatric population: Time in therapeutic range, initial and stable dosing, and adverse effects
Gene: VKORC1
Variant/haplotype: rs9923231
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele T is associated with decreased dose of warfarin in children as compared to allele C.
Notes: with an approximate decrease of daily dose of 0.66mg.
Article: Human Polymorphisms in the Glutathione Transferase Zeta 1/Maleylacetoacetate Isomerase Gene Influence the Toxicokinetics of Dichloroacetate
Gene: GSTZ1, POMT2
Variant/haplotype: rs1046428
Drug(s): dichloroacetic acid
Phenotype category: Other, Metabolism/PK
Significant: yes
Association: Allele C is associated with increased clearance of dichloroacetic acid in healthy individuals.
Notes: The statement above  is meant for a haplotype rather than for the allele.  For the various possible haplotype combinations involving rs7975,rs7972,rs1046428, the most rapid clearance was observed for subjects having at least one "wild-type" allele (G for rs7975,G for rs7972, C for rs1046428. Rate was 2.2 +/- 0.7 vs 0.73 +/- 0.84 mL/min, and the very highest rate was seen in homozygous "wild-type".
Article: Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder
Gene: PYROXD2
Variant/haplotype: rs1061115
Drug(s): methylphenidate
Phenotype category: Efficacy
Significant: no
Association: Allele G 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: Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population
Gene: VKORC1
Variant/haplotype: rs61742245
Drug(s): warfarin
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of warfarin as compared to allele C.
Notes: Neither the addition of race, number of concurrent medications nor the number of concurrent medications interacting with warfarin enhanced algorithm performance. Similarly, consideration of CYP4F2, CALU or GGCX variant genotypes did not improve algorithms.
Article: Association of ABCB1 Gene Polymorphisms with Efficacy and Adverse Reaction to Risperidone or Paliperidone in Han Chinese Schizophrenic Patients
Gene: ABCB1
Variant/haplotype: rs1128503
Drug(s): risperidone
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AG + GG are not associated with response to risperidone in people with Schizophrenia as compared to genotype AA.
Notes: Alleles given as reverse strand C and T. Efficacy measured with reduction in PANSS total score reduced rate.
Article: CYP2D6 polymorphisms and endoxifen concentration in Chinese patients with breast cancer
Gene: CYP2D6
Variant/haplotype: CYP2D6 normal metabolizer
Drug(s): endoxifen
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2D6 normal metabolizer is associated with increased concentrations of endoxifen in women with Breast Neoplasms as compared to CYP2D6 intermediate metabolizer.
Notes: "Endoxifen concentration was not significantly different among different AS groups (p = 0.106)...And the median endoxifen concentration was higher in CYP2D6 phenotype NM (18ng/ml, 95%CI 18–24 ng/ml) than in IM (13ng/ml, 95%CI 13–18 ng/ml, p = 0.0077, Fig. 2). A similar situation was found with MRE/Tam (p < 0.0001)."
Article: Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia
Gene: SLC19A1
Variant/haplotype: rs1131596
Drug(s): methotrexate
Phenotype category: Efficacy
Significant: no
Association: Allele G is not associated with response to methotrexate in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to allele A.
Notes: Please note: alleles have been complemented to the + chromosomal strand.