Naslov
Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks : a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies

Autori
Yu, B. ; Barbalić, Maja

Izvornik
Circulation. Cardiovascular genetics (1942-325X) 6 (2013), 1; 82-88

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
genetics ; genome-wide association study ; troponin

Sažetak
High levels of cardiac troponin T measured by a highly sensitive assay (hs-cTnT) are strongly associated with incident coronary heart disease (CHD) and heart failure (HF). No large-scale genome-wide association study (GWAS) of hs-cTnT has been reported to date. We sought to identify novel genetic variants that are associated with hs-cTnT levels. Methods and Results We performed a GWAS in 9, 491 European-Americans and 2, 053 African-Americans free of CHD and HF from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). GWASs were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum, and then across race strata to produce overall estimates and p- values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374, p = 9.06 × 10−9) near the nuclear receptor coactivator 2 (NCOA2) gene. Over-expression of NCOA2 can be detected in myoblasts An additional analysis using logistic regression and the clinically motivated 99th percentile cut-point detected a significant association at 1q32 (rs10091374, p = 9.06 × 10−8) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated SNPs were not associated with CHD in a large case- control study, but rs12564445 was significantly associated with incident HF in ARIC European- Americans (HR = 1.16, p-value = 0.004). Conclusions We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.

Izvorni jezik
Engleski

Napomena
CARDIoGRAM Consortium ; ISSN 1942-325X (u CC-u).

POVEZANOST RADA