shlokn/autogkb huggingface dataset:
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: yes
Association: Genotypes CT + TT are associated with increased response to buprenorphine in people with Opioid-Related Disorders as compared to genotype CC.
Notes: This was found in European Americans only. The opposite association was found in African Americans but was not statistically significant.
Article: The Pharmacogenetics of NAT2 Enzyme Maturation in Perinatally HIV Exposed Infants Receiving Isoniazid
Gene: NAT2
Variant/haplotype: NAT2*1, NAT2*4, NAT2*6, NAT2*7, NAT2*14, NAT2*16
Drug(s): isoniazid
Phenotype category: Metabolism/PK
Significant: not stated
Association: NAT2 *16 + *6 + *7 + *14 is associated with decreased clearance of isoniazid in children with HIV Infections as compared to NAT2 *4 + *1.
Notes: Fast acetylators (two fast alleles NAT2*4, *12, *13) (originally annotated as *4, *12A, *13A) were grouped together, compared to intermediate (one fast and one slow allele) and slow acetylators (two slow alleles NAT2*5, *6, *7, *14) (originally annotated as *5A, *6B, *7A, *14A) in an analysis of clearance of isoniazid in infants over time from 3 months old to 24 months (normalized for 70kg body weight). Fast acetylators displayed an increase in clearance over this time period, also seen in intermediate acetylators but in slow acetylators clearance remained constant over time.; The arylamine N-acetyltransferases (NATs) database was transitioned into the PharmVar database in March 2024. The alleles in included in this annotation are mapped as following: NAT2*12A under the *1 core allele; NAT2*13A under the *4 core allele; NAT2*14A under the *14 core allele; NAT2*5A under the *16 core allele; ; NAT2*6B under the *6 core allele; NAT2*7A under the *7 core allele.
Article: A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients
Gene: F2
Variant/haplotype: rs3136516
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: Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients
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.
Article: Implementation of Clinical Cytochrome P450 3A Genotyping for Tacrolimus Dosing in a Large Kidney Transplant Program
Gene: CYP3A5
Variant/haplotype: CYP3A5 intermediate metabolizer and normal metabolizer
Drug(s): tacrolimus
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: CYP3A5 normal metabolizer and intermediate metabolizer is associated with increased time to response to tacrolimus in people with Kidney Transplantation as compared to CYP3A5 poor metabolizer.
Notes: Study measured "CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272), CYP3A5*7 (rs41303343).and alleles were assigned metabolizer; categories according to CPIC guidelines. " "The time totherapeutic tacrolimus trough concentrations was 6.6 ± 0.6 days for normal/intermediate; metabolizers and 3.6 ± 0.3 days for poor metabolizers." "The; percent of patient tacrolimus trough concentrations within the desired range was 33% for normal/intermediate metabolizers and 42% for poor metabolizers"
Article: Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid‐Treated Oncology Patients
Gene: CYP2D6
Variant/haplotype: CYP2D6 poor metabolizers and intermediate metabolizers
Drug(s): codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol
Phenotype category: Efficacy
Significant: yes
Association: CYP2D6 intermediate metabolizer and poor metabolizer are associated with decreased response to codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone or tramadol in people with Neoplasms and Pain as compared to CYP2D6 normal metabolizer.
Notes: IM or PM patients were more likely to require a pain-related procedure or hospital encounter and had increased exposure to morphine or hydromorphone, presumably as a result of inadequate analgesia by CYP2D6-metabolized opioids. 93% of IM or PM patients received a CYP2D6-metabolized opioid (codeine, tramadol, oxycodone, hydrocodone). Patients with a CYP2D6 AS of 1 were assigned as NM rather than IM. Authors also considered phenoconversion and reduced AS accordingly in patients taking concomitant CYP2D6 inhibitors.
Article: Variation in the Alpha 5 Nicotinic Acetylcholine Receptor Subunit Gene Predicts Cigarette Smoking Intensity as a Function of Nicotine Content
Gene: CHRNA5
Variant/haplotype: rs16969968
Drug(s): nicotine
Phenotype category: Other
Significant: yes
Association: Genotype GG is associated with decreased dose of nicotine in people with Tobacco Use Disorder as compared to genotypes AA + AG.
Notes: Genotype GG is associated with decreased total puff volume when exposed to nicotine compared to cigarettes containing placebo in people with Tobacco Use Disorder as compared to genotypes AA + AG.
Article: Escitalopram pharmacogenetics: CYP2C19 relationships with dosing and clinical outcomes in Autism Spectrum Disorder
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): escitalopram
Phenotype category: Efficacy
Significant: no
Association: CYP2C19 *1/*2 + *2/*2 are not associated with response to escitalopram in people with Autistic Disorder as compared to CYP2C19 *1/*1.
Notes: No difference was found between the metabolizer groups (intermediate/poor metabolizer; extensive metabolizer or ultra rapid metabolizer). *3 was genotyped but no carrier identified. *2/*2 N=1 and was grouped with *1/*2. *1/*17 and *17/*17 were grouped together as UM.
Article: A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism
Variant/haplotype: rs113288603
Drug(s): nicotine
Phenotype category: Metabolism/PK
Significant: yes
Association: Allele T is associated with decreased clearance of nicotine as compared to allele C.
Notes: The minor allele was independently associated with decreased NMR, indicating decreased rate of nicotine clearance. rs56113850 and rs12461964 were in LD with CYP2A6*2, and esv2663194 (not annotated) was in LD with CYP2A6*9. rs56113850, rs12461964, and esv2663194 emerged as signals independently associated with NMR in GWAS and in conditional analyses. A fourth signal, rs113288603, was not significant in GWAS, but was significant after conditioning on the top associated SNP, rs56113850.
Article: Novel Single Nucleotide Polymorphisms in Interleukin 6 Affect Tacrolimus Metabolism in Liver Transplant Patients
Gene: CYP3A5
Variant/haplotype: rs776746
Drug(s): tacrolimus
Phenotype category: Dosage, Metabolism/PK
Significant: yes
Association: Genotypes CT + TT are associated with increased dose of tacrolimus in people with liver transplantation as compared to genotype CC.
Notes: At 1, 3, 4 weeks post-transplantation, The C/D values of tacrolimus in both donors and recipients expressing CYP3A5 were lower than those not expressing CYP3A5.
Article: Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
Gene: CYP3A5
Variant/haplotype: CYP3A5 poor metabolizer and intermediate metabolizer genotypes
Drug(s): 4-hydroxytamoxifen
Phenotype category: Metabolism/PK
Significant: no
Association: CYP3A5 poor metabolizer and intermediate metabolizer genotypes are not associated with concentrations of 4-hydroxytamoxifen in women with Breast Neoplasms.
Article: Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2
Drug(s): rabeprazole
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP2C19 *1/*1 is associated with increased metabolism of rabeprazole in healthy individuals as compared to CYP2C19 *2/*2.
Notes: Healthy individuals with the *1/*1 genotype had lower area under the concentration-time curve (AUC) for rabeprazole, as compared to those with the *2/*2 genotype. Subjects were given rabeprazole for 8 days; AUC was measured on day 1 and day 8 after rabeprazole administration. Please note that the *2 allele was referred to by its previous designation (CYP2C19*m1).
Article: The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population
Gene: ABCB1
Variant/haplotype: rs1045642
Drug(s): clopidogrel
Phenotype category: Efficacy
Significant: yes
Association: Genotype GG is associated with increased resistance to clopidogrel in people with Hypertension as compared to genotype AA.
Notes: There was no significant association between rs1045642 and the risk of clopidogrel resistance across the whole study cohort (p=0.288).; Genotype GG is associated with resistance to clopidogrel in people without hypoproteinaemia as compared to genotype AA (p=0.045).; Allele G is associated with increased resistance to clopidogrel in patients with hypertension compared to allele A (p=0.040) and in patients without hypoproteinaemia compared to allele A (p=0.033).; Genotypes AA + GG are not associated with resistance to clopidogrel in people with hypertension as compared to genotype AA (p=0.085) or in people without hypoproteinaemia as compared to genotype AA (p=0.644).; Genotype GG is not associated with resistance to clopidogrel in people with hypertension as compared to genotype AA+AG (p=0.104) or in people without hypoproteinaemia as compared to genotype AA (p=0.153).; Please note that alleles have been complemented to the positive strand.
Article: Effects of CYP2C19 Loss-of-Function Variants on the Eradication of H. pylori Infection in Patients Treated with Proton Pump Inhibitor-Based Triple Therapy Regimens: A Meta-Analysis of Randomized Clinical Trials
Gene: CYP2C19
Variant/haplotype: CYP2C19*1, CYP2C19*2, CYP2C19*3
Drug(s): lansoprazole
Phenotype category: Efficacy
Significant: yes
Association: CYP2C19 *1/*1 is associated with decreased response to lansoprazole in people with Helicobacter Infections as compared to CYP2C19 *2/*2 + *2/*3 + *3/*3.
Notes: Subjects with the *1/*1 genotype had a significantly lower eradication rate of Helicobacter pylori (H. pylori), as compared to those with the *2/*2, *2/*3 or *3/*3 genotype. This was a meta-analysis and included 9 studies. Patients were treated with the drugs anywhere from 7-14 days, and also received the antibiotics amoxicillin and clarithromycin as part of triple therapy.
Article: Effect of A118G (rs1799971) single‐nucleotide polymorphism of the μ‐opioid receptor OPRM1 gene on intraoperative remifentanil requirements in Japanese women undergoing laparoscopic gynecological surgery
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): acetaminophen
Phenotype category: Dosage
Significant: yes
Association: Genotypes AG + GG is associated with increased dose of acetaminophen in women with Pain, Postoperative as compared to genotype AA.
Notes: This is after laparoscopic gynecological surgery where there was propofol and remifentanil infusion. "The number of periodic postoperative acetaminophen doses that were required during 24 h was significantly higher in patients with the AG genotype than the AA genotype (p = 0.039) and in patients with the AG or GG genotype than the AA genotype (p = 0.040; Table 1). Other pain-related phenotypes, including the initial fentanyl bolus dose, PCA fentanyl consumption dose, total postoperative fentanyl dose (Figure 1D), number of patients who required rescue analgesics, and average NRS pain score, were not different among or between patients with any different genotype (Table 1)."
Article: Pharmacogenetic Approach to Tramadol Use in the Arab Population
Gene: OPRM1
Variant/haplotype: rs1799971
Drug(s): tramadol
Phenotype category: Efficacy
Significant: no
Association: Genotype AG is not associated with increased clinical benefit to tramadol in people with Pain, Postoperative as compared to genotype AA.
Notes: "The basal pain score showed a statistically significant difference between subject groups, with the details of OPRM1 G118G for 9.14 and OPRM1 G118A for 8.04 (p < 0.01) in this study (Figure 3). However, such a difference was not observed for the analgesic effect of tramadol (ΔNRS) between these genotype groups in this study (Table 2)." "No homozygous OPRM1 G/G genotype was found in this study."
Article: Effects of a Common Eight Base Pairs Duplication at the Exon 7-Intron 7 Junction on Splicing, Expression, and Function of OCT1
Gene: SLC22A1
Variant/haplotype: rs1349294037
Drug(s): fenoterol
Phenotype category: Other
Significant: not stated
Association: Genotype TAAGTTGT/TAAGTTGT is not associated with increased concentrations of fenoterol as compared to genotype del/del.
Notes: "Even more, the AUC of fenoterol was not higher in homozygous carriers of the rs35854239 duplication allele compared to the wild-type (means of 84.25 vs. 86.84 min × ng/ml, respectively; Figure 7B). In comparison, poor OCT1 transporters showed 1.89-fold higher AUCs for fenoterol. This data suggests that compared to the well-known loss-of-function coding variants, the 8 bp duplication shows only limited effects on drugs pharmacokinetics." rs35854239 was retired by dbSNP. Authors also described two other rs numbers for this indel (rs113569197 or rs36056065) also retired. We mapped this to 3 possible dbSNP identifiers that all represent indels near the end of exon 7, rs1349294037, rs755473306 and rs2114790299 but none seems to represent exactly the variants depicted in figure 1.
Article: Increased Risk of Vincristine Neurotoxicity Associated with Low CYP3A5 Expression Genotype in Children with Acute Lymphoblastic Leukemia
Gene: CYP3A5
Variant/haplotype: CYP3A5*1, CYP3A5*3
Drug(s): vincristine
Phenotype category: Metabolism/PK
Significant: yes
Association: CYP3A5 *1/*3 is associated with increased metabolism of vincristine in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to CYP3A5 *3/*3.
Notes: CYP3A5 *1/*3 individuals produced significantly more of the M1 vincristine metabolite compared to *3/*3 individuals (1286 +/- 1068 pg/ml vs. 329 +/- 277 pg/ml).; The metabolic ratio of vincristine/M1 was also significantly higher in *3/*3 as compared to *1/*3.
Article: Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients
Gene: DRD3
Variant/haplotype: rs6280
Drug(s): risperidone
Phenotype category: Efficacy
Significant: no
Association: Allele C is associated with decreased response to risperidone in people with Schizophrenia as compared to allele T.
Notes: The C allele was initially significantly more frequent in patients designated as non-responders to risperidone (i.e. <50% reduction in PANSS score compared to the cohort average). However, significance was lost following correction for multiple testing.
Article: Population Pharmacokinetic/Pharmacogenetic Model for Optimization of Efavirenz Therapy in Caucasian HIV-Infected Patients
Gene: CYP2B6
Variant/haplotype: CYP2B6*1, CYP2B6*2
Drug(s): efavirenz
Phenotype category: Metabolism/PK
Significant: no
Association: CYP2B6 *2 is not associated with concentrations of efavirenz in people with HIV as compared to CYP2B6 *1/*1.
Article: Phase I study of irinotecan and doxifluridine for metastatic colorectal cancer focusing on the UGT1A1*28 polymorphism
Gene: UGT1A1
Variant/haplotype: UGT1A1*1, UGT1A1*28
Drug(s): SN-38
Phenotype category: Metabolism/PK
Significant: yes
Association: UGT1A1 *1/*28 is associated with increased concentrations of SN-38 in people with Colorectal Neoplasms and Neoplasm Metastasis as compared to UGT1A1 *1/*1.
Notes: "Patients with the heterozygous genotype (TA6/TA7) had significantly higher AUC0–∞ SN‐38, maximum concentration of SN‐38, half‐life period of SN‐38, and lower total clearance of SN‐38 values compared to the wild‐type genotype (TA6/TA6). " "These data were collected from patients at level 2 at which the irinotecan dose was 100 mg/m2"
Article: Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients
Gene: CYP2C9
Variant/haplotype: rs1057910
Drug(s): warfarin
Phenotype category: Dosage
Significant: yes
Association: Allele C is associated with decreased dose of warfarin as compared to allele A.
Notes: This SNP defines CYP2C9*3. CYP2C9 *2,*3,*4,*5,*8 were grouped into three groups for testing: *1/*1 vs. *1/*2 + *1/*3 + *1/*4 + *1/*5 + *1/*8 vs *2/*2 + *2/*3 + *3/*3 + *5/*5. People having one or two variant alleles had lower dose requirements than people who were *1/*1.
Article: Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics
Gene: SLC26A9
Variant/haplotype: rs7512462
Drug(s): ivacaftor
Phenotype category: Efficacy
Significant: yes
Association: Genotypes CC + CT is associated with increased response to ivacaftor in children with Cystic Fibrosis as compared to genotype TT.
Notes: Patients had a gating mutation that caused cystic fibrosis (G551D). Response was measured with change in FEV1.
Article: RRM1 and RRM2 pharmacogenetics: association with phenotypes in HapMap cell lines and acute myeloid leukemia patients
Gene: RRM1
Variant/haplotype: rs2898950
Drug(s): cladribine, cytarabine
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AC + CC is associated with increased response to cladribine and cytarabine in children with Leukemia, Myeloid, Acute as compared to genotype AA.
Notes: Less patients with a complete response after the first induction therapy were seen in the AA genotype group. No multiple testing adjustments were performed: 7 SNPs were investigated.
Article: High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients
Gene: ABCG2
Variant/haplotype: rs12505410
Drug(s): imatinib
Phenotype category: Efficacy
Significant: yes
Association: Genotypes GG + GT is associated with increased response to imatinib in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive as compared to genotype TT.
Notes: Individuals with the GG or GT genotype had a higher cumulative incidence of major molecular response (CI-MMR, estimated using Sokal score) after 18 months of treatment with a 400mg/day dose of imatinib, as compared to those with the TT genotype. No significant results were seen when considering patients taking a 600mg/day dose (n=107; p=0.32), though significant results were seen when considering all patients (n=239; p=0.045). The authors note that they used the Benjamini and Hochberg method for multiple testing issues.
Article: The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer
Gene: CCND1
Variant/haplotype: rs9344
Drug(s): lapatinib
Phenotype category: Efficacy
Significant: no
Association: Genotypes CA/CA + CA/CG are associated with increased response to lapatinib in women with Breast Neoplasms as compared to genotype CG/CG.
Notes: The genotype association was not significant in univariate analysis but when looking at A carriers those on capecitabine plus lapatinib did significantly better than those on capecitabine alone whereas for the G homozygotes the outcomes were similar for both drug combinations.
Article: β2-Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies
Gene: ADRB2
Variant/haplotype: rs1800888
Drug(s): atenolol, metoprolol
Phenotype category: Efficacy
Significant: no
Association: Allele T is not associated with response to atenolol or metoprolol in people with Tachycardia as compared to allele C.
Notes: No significant association between this variant and response to atenolol or metoprolol, as measured by changes in heart rate, in black or white patients. Note that this variant was not analyzed in black patients from the INVEST cohort as the minor allele was not detected in these patients.
Article: Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction
Gene: NTRK2
Variant/haplotype: rs4358872
Drug(s): methadone
Phenotype category: Dosage
Significant: no
Association: Genotype GG is associated with decreased dose of methadone in people with Heroin Dependence as compared to genotypes GT + TT.
Notes: This association was statistically significant after permutation analysis based on 40,000 replicates, but not statistically significant after adjusting for testing for multiple SNPs (Bonferroni correction). Note; this SNP was in LD with rs1948308, rs2378676, and rs4877900 (r^2>0.7).
Article: Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study
Gene: ADCY1
Variant/haplotype: rs1521470
Drug(s): lithium
Phenotype category: Efficacy
Significant: yes
Association: Allele A is associated with decreased response to lithium in people with Bipolar Disorder as compared to allele G.
Article: Association studies of dopamine synthesis and metabolism genes with multiple phenotypes of heroin dependence
Gene: DDC
Variant/haplotype: rs11575553
Drug(s): heroin
Phenotype category: Dosage
Significant: no
Association: Allele A is not associated with dose of heroin in people with Heroin Dependence as compared to allele G.
Article: Association between single nucleotide polymorphisms in DNA repair genes and the efficacy of radiotherapy in nasopharyngeal carcinoma patients
Gene: XRCC3
Variant/haplotype: rs861539
Drug(s): radiotherapy
Phenotype category: Efficacy
Significant: no
Association: Allele A is not associated with response to radiotherapy in people with Nasopharyngeal Neoplasms as compared to allele G.
Notes: alleles complemented compared to what is shown in the paper. Authors state "Thr241Met polymorphism may act as a prognostic indicator for NPC patients treated with radiotherapy" as OS was better for heterozygotes.
Article: Assessing the Contribution of Opioid- and Dopamine-Related Genetic Polymorphisms to the Abuse Liability of Oxycodone
Gene: COMT
Variant/haplotype: rs4680
Drug(s): oxycodone
Phenotype category: Efficacy
Significant: yes
Association: Genotypes AA + AG are associated with increased response to oxycodone as compared to genotype GG.
Notes: Subjects with the AA or AG genotypes had an increased subjective 'Stimulated' response to oxycodone than subjects with the GG genotype.
Article: Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma
Gene: KDR
Variant/haplotype: rs2305948
Drug(s): sunitinib
Phenotype category: Efficacy
Significant: no
Association: Genotype CT is not associated with response to sunitinib in people with Carcinoma, Renal Cell as compared to genotype CC.
Notes: The genotype was not associated with clinical benefit, which was defined as either partial response or stable disease. The genotype was also not associated with progression free survival, or overall survival.