Circulating n-3 fatty acids and trans-fatty acids, PLA2G2A gene variation and sudden cardiac arrest.
Whether genetic factors influence the associations of fatty acids with the risk of sudden cardiac arrest (SCA) is largely unknown. To investigate possible gene-fatty acid interactions on SCA risk, we used a case-only approach and measured fatty acids in erythrocyte samples from 1869 SCA cases in a population-based repository with genetic data. We selected 191 SNP in ENCODE-identified regulatory regions of fifty-five candidate genes in fatty acid metabolic pathways. Using linear regression and additive genetic models, we investigated the association of the selected SNP with erythrocyte levels of fatty acids, including DHA, EPA and trans-fatty acids among the SCA cases. The assumption of no association in non-cases was supported by analysis of publicly available datasets containing over 8000 samples. None of the SNP-fatty acid associations tested among the cases reached statistical significance after correction for multiple comparisons. One SNP, rs4654990 near PLA2G2A, with an allele frequency of 0·33, was nominally associated with lower levels of DHA and EPA and higher levels of trans-fatty acids. The strongest association was with DHA levels (exponentiated coefficient for one unit (1 % of total fatty acids), 0·90, 95 % CI 0·85, 0·97; P = 0·003), indicating that for subjects with a coded allele, the OR of SCA associated with one unit higher DHA is about 90 % what it is for subjects with one fewer coded allele. These findings suggest that the associations of circulating n-3 and trans-fatty acids with SCA risk may be more pronounced in carriers of the rs4654990 G allele.
Cardiovascular Health Research Unit , Department of Medicine , University of Washington , Seattle, WA , USA.
Rozenn N
RN
Lemaitre
Cardiovascular Health Research Unit , Department of Biostatistics , University of Washington , Seattle, WA , USA.
Traci M
TM
Bartz
Department of Internal Medicine , University of New Mexico , Albuquerque, NM , USA.
Irena B
IB
King
Cardiovascular Health Research Unit , Department of Medicine , University of Washington , Seattle, WA , USA.
Jennifer A
JA
Brody
Cardiovascular Health Research Unit , Department of Biostatistics , University of Washington , Seattle, WA , USA.
Barbara
B
McKnight
Cardiovascular Health Research Unit , Department of Medicine , University of Washington , Seattle, WA , USA.
Nona
N
Sotoodehnia
Cardiovascular Health Research Unit , Department of Medicine , University of Washington , Seattle, WA , USA.
Thomas D
TD
Rea
Cardiovascular Health Research Unit , Department of Medicine , University of Washington , Seattle, WA , USA.
Catherine O
CO
Johnson
Friedman School of Nutrition Science and Policy , Tufts University , Boston, MA , USA.
Dariush
D
Mozaffarian
Cardiovascular Research Institute and Institute for Human Genetics , University of California , San Francisco, CA , USA.
Stephanie
S
Hesselson
Cardiovascular Research Institute and Institute for Human Genetics , University of California , San Francisco, CA , USA.
Pui-Yan
PY
Kwok
New York Academy of Medicine , New York, NY , USA.
David S
DS
Siscovick
Epidemiology; Fatty acids; Genetics; SCA, sudden cardiac arrest; Sudden cardiac arrest; sPLA2, secretory phospholipase A2