Expressive

rs1142345 - TPMT

Magnitude 4.5 · 4 studies on file

Reported associations

  • Genome-Wide Association Study for the Genetic Determinants of Thiopurine Methyltransferase Protein Expression in Human Livers and Racial Differences. - Pharmaceutical research (2023) · Smith LS, Wang X, Shi J, He B, Zhu HJ · PubMed 37430149

    Polymorphisms in the Thiopurine S-Methyltransferase (TPMT) gene are associated with decreased TPMT activity, but little is known about their impact on TPMT protein expression in the liver. This project is to conduct a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with altered TPMT protein expression in human livers and to determine if demographics affect hepatic TPMT protein expression. Human liver samples (n = 287) were genotyped using a whole genome genotyping panel and quantified for TPMT protein expression using a Data-Independent Acquisition proteomics approach. Thirty-one SNPs were found to be associated with differential expression of TPMT protein in the human livers. Subsequent analysis, conditioning on rs1142345, a SNP assoc

  • Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia - Unknown journal (n.d.) · Unknown authors · PubMed 36580335

    ABSTRACT: Key Points Question What are the genetic drivers of interpatient variability in the occurrence of hepatotoxic effects during treatment for acute lymphoblastic leukemia (ALL)? Findings In this genetic association study of 3557 children, adolescents, and young adults receiving ALL therapy, variants in UGT1A1 and PNPLA3 were associated with hyperbilirubinemia and elevated alanine aminotransferase and aspartate aminotransferase levels, respectively. A polygenic risk score-based analysis demonstrated that the UGT1A1 variant was the primary driver of elevated bilirubin levels, while other genetic variants contributed to aminotransferase levels even after adjusting for PNPLA3. Meaning These findings suggest that there is an association between genetic factors and interpatient variabil

  • Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging - Unknown journal (n.d.) · Unknown authors · PubMed 34187551

    ABSTRACT: Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metaboli

  • A Genome-wide Approach Validates that Thiopurine Methyltransferase Activity is a Monogenic Pharmacogenomic Trait - Unknown journal (n.d.) · Unknown authors · PubMed 27564568

    ABSTRACT: We performed a genome-wide association study of primary erythrocyte TPMT activity in children with leukemia (n = 1026). Adjusting for age and ancestry, TPMT was the only gene that reached genome-wide significance (top hit rs1142345 or 719A>G, P = 8.6 × 10−61). Additional genetic variants (besides the 3 SNPs rs1800462, rs1800460 and rs1142345 defining TPMT clinical genotype) did not significantly improve classification accuracy for TPMT phenotype. Clinical mercaptopurine tolerability in 839 patients was related to TPMT clinical genotype (P = 2.4 × 10−11). Using 177 lymphoblastoid cell lines (LCLs), there were 251 SNPs ranked higher than the top TPMT SNP (rs1142345 P = 6.8 × 10−5), showing the limitation of LCLs for pharmacogenomic discovery. In a GWAS, TPMT activity in pa

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