Genome-wide significant locus of beta-trace protein, a novel kidney function biomarker, identified in European and African Americans

Adrienne Tin, Brad C. Astor, Eric Boerwinkle, Ron C. Hoogeveen, Josef Coresh, W. H.Linda Kao

Research output: Contribution to journalArticle

Abstract

BackgroundBeta-trace protein (BTP), measured in serum or plasma, has potential as a novel biomarker for kidney function. Little is known about the genes influencing BTP levels.MethodsWe conducted a genome-wide association study of log-transformed plasma BTP levels in 6720 European Americans (EAs) and replicated the significant associations in 1734 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study.ResultsWe identified a genome-wide significant locus in EA upstream of Prostaglandin D2 synthase (PTGDS), the gene encoding BTP. Each copy of the A allele at rs57024841 was associated with 5% higher BTP levels (P =1.2 × 10-23). The association at PTGDS was confirmed in AAs (6% higher BTP for each A allele at rs57024841, P =1.9 × 10-7). The index single nucleotide polymorphisms (SNPs) in EAs and AAs explained ∼1.1% of the log(BTP) variance within each population and explained over 30% of the difference in log(BTP) levels between EAs and AAs. The index SNPs at the PTGDS locus in the two populations were not associated with the estimated glomerular filtration rate (eGFR) or the urine albumin creatinine ratio (P > 0.05). We further tested for the associations of BTP with 16 known loci of the eGFR in EA, and BTP was associated with 3 of 16 tested.ConclusionsThe identification of a novel BTP-specific (non-renal related) locus and the confirmation of several genetic loci of the eGFR with BTP extend our understanding of the metabolism of BTP and inform its use as a kidney filtration biomarker.

Original languageEnglish (US)
Pages (from-to)1497-1504
Number of pages8
JournalNephrology Dialysis Transplantation
Volume28
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Chronic kidney disease
  • GWAS
  • Genome-wide association study
  • Glomerular filtration rate
  • Kidney function biomarker

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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