biostudies-literatureTin ANIDDK NIH HHSNCRR NIH HHSNHLBI NIH HHSNHGRI NIH HHSPHS HHS1497-504https://www.ebi.ac.uk/biostudies/studies/S-EPMC3685304biostudies-literatureUnknown28(6)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal AssociationGenome-wide significant locus of beta-trace protein, a novel kidney function biomarker, identified in European and African Americans.PMC3685304HHSN268‐201100006CHHSN2682‐01100011CR01 DK076770U01 HG004402HHSN268200625226CUL1RR025005R01 DK076770-01R01HL59367HHSN268201100005CHHSN268201100008CU01HG004402HHSN268201100007CUL1 RR025005HHSN268201100009CHHSN268201100010CR01HL087641R01 HL086694R01HL086694R01 HL087641HHSN268201100012CCoresh JHoogeveen RCAstor BCBoerwinkle ETin AKao WHfalseGenome-wide significant locus of beta-trace protein, a novel kidney function biomarker, identified in European and African Americans.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.2013-01-01T00:00:00Z2013 Jun2024-11-15T22:31:51.615Z2019-03-27T01:11:47ZS-EPMC36853042332870710.1093/ndt/gfs591