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.