Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest

Heart Rhythm. 2014 Mar;11(3):471-7. doi: 10.1016/j.hrthm.2014.01.008. Epub 2014 Jan 10.

Abstract

Background: There is limited information on genetic factors associated with sudden cardiac arrest (SCA).

Objective: To assess the association of common variation in genes in fatty acid pathways with SCA risk.

Methods: We selected 85 candidate genes and 1155 single nucleotide polymorphisms (SNPs) tagging common variation in each gene. We investigated the SNP associations with SCA in a population-based case-control study. Cases (n = 2160) were from a repository of SCA in the greater Seattle area. Controls (n = 2615), frequency-matched on age and sex, were from the same area. We used linear logistic regression to examine SNP associations with SCA. We performed permutation-based p-min tests to account for multiple comparisons within each gene. The SNP associations with a corrected P value of <.05 were then examined in a meta-analysis of these SNP associations in 9 replication studies totaling 2129 SCA cases and 23,833 noncases.

Results: Eight SNPs in or near 8 genes were associated with SCA risk in the discovery study, one of which was nominally significant in the replication phase (rs7737692, minor allele frequency 36%, near the LPCAT1 gene). For each copy of the minor allele, rs7737692 was associated with 13% lower SCA risk (95% confidence interval -21% to -5%) in the discovery phase and 9% lower SCA risk (95% confidence interval -16% to -1%) in the replication phase.

Conclusions: While none of the associations reached significance with Bonferroni correction, a common genetic variant near LPCAT1, a gene involved in the remodeling of phospholipids, was nominally associated with incident SCA risk. Further study is needed to validate this observation.

Keywords: Death; Genetic epidemiology; Sudden.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 1-Acylglycerophosphocholine O-Acyltransferase / genetics*
  • Aged
  • Algorithms
  • Alleles
  • Case-Control Studies
  • Death, Sudden, Cardiac*
  • Fatty Acids / genetics*
  • Fatty Acids / metabolism
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • Fatty Acids
  • 1-Acylglycerophosphocholine O-Acyltransferase
  • Lpcat1 protein, human

Grant support