Format

Send to

Choose Destination
J Cardiovasc Electrophysiol. 2014 Nov;25(11):1150-7. doi: 10.1111/jce.12483. Epub 2014 Aug 25.

A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans.

Author information

1
Department of Medicine, Division of Cardiology, Section of Electrophysiology, Northwestern University, Chicago, Illinois, USA.

Abstract

OBJECTIVE:

We examined the association of rs7626962 (S1103Y) or rs7629265, a variant in high linkage disequilibrium with S1103Y (r(2) = 0.87 - 1), with sudden cardiac death (SCD) and atrial fibrillation (AF) among African Americans.

BACKGROUND:

The SCN5A missense variant S1103Y has been associated with SCD among African Americans in small case-control studies, but larger population-based studies are needed to validate these findings. The association of this variant with AF has not been fully explored.

METHODS:

Using genotyping data on over 7,000 African Americans from 5 cohorts (Atherosclerosis Risk in Communities [ARIC], Cleveland Family Study [CFS], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], Cardiovascular Health Study [CHS]), we examined the association of rs7629265 with electrocardiographic PR, QRS, and QT intervals, and with incident AF and SCD. We examined association of S1103Y (rs7626962) with SCD using a population-based case-control study of SCD Cardiac Arrest Blood Study (CABS).

RESULTS:

Meta-analyses across 5 cohorts demonstrated that rs7629265 was significantly associated with PR duration (β = -4.1 milliseconds; P = 2.2×10(-6) ), but not significantly associated with QRS or QT intervals. In meta-analyses of prospectively followed ARIC and CHS participants (n = 3,656), rs7629265 was associated with increased AF risk (n = 299 AF cases; HR = 1.74, P = 1.9 × 10(-4) ). By contrast, rs7629265 was not significantly associated with SCD risk in ARIC (n = 83 SCD cases; P = 0.30) or CHS (n = 54 SCD cases; P = 0.47). Similarly, S1103Y was not significantly associated with SCD risk in CABS (n = 225 SCD cases; P = 0.29).

CONCLUSION:

The common SCN5A variant, rs7629265, is associated with increased AF risk and shorter PR interval among African Americans. In contrast to prior reports, we found no evidence of association of rs7629265 or rs7626962 (S1103Y) with SCD risk in the general population.

KEYWORDS:

PR interval; atrial fibrillation; electrocardiogram; genetics; sudden death

PMID:
25065297
PMCID:
PMC4454499
DOI:
10.1111/jce.12483
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center