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

TitleGenome-wide significant locus of beta-trace protein, a novel kidney function biomarker, identified in European and African Americans.
Publication TypeJournal Article
Year of Publication2013
AuthorsTin A, Astor BC, Boerwinkle E, Hoogeveen RC, Coresh JJ
Secondary AuthorsKao LWH
JournalNephrol Dial Transplant
Volume28
Issue6
Pagination1497-504
Date Published2013 Jun
ISSN1460-2385
KeywordsAfrican Americans, Aged, Albuminuria, Biomarkers, Diabetes Mellitus, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Hypertension, Intramolecular Oxidoreductases, Kidney, Kidney Function Tests, Lipocalins, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Prospective Studies
Abstract

BACKGROUND: Beta-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.

METHODS: We 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.

RESULTS: We 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.

CONCLUSIONS: The 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.

DOI10.1093/ndt/gfs591
Alternate JournalNephrol Dial Transplant
PubMed ID23328707
PubMed Central IDPMC3685304
Grant ListUL1RR025005 / RR / NCRR NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HHSN268‐201100006C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN2682‐01100011C / / PHS HHS / United States
R01 DK076770 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 DK076770-01 / DK / NIDDK NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States