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

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.

• Authors: Rozenn N Lemaitre, Catherine O Johnson, Stephanie Hesselson, Nona Sotoodehnia, Nona Sotoodhenia, Barbara McKnight, Colleen M Sitlani, Thomas D Rea, Irena B King, Pui-Yan Kwok, Angel Mak, Guo Li, Jennifer Brody, Eric Larson, Dariush Mozaffarian, Bruce M Psaty, Adriana Huertas-Vazquez, Jean-Claude Tardif, Christine M Albert, Leo-Pekka Lyytikäinen, Dan E Arking, Stefan Kääb, Heikki V Huikuri, Bouwe P Krijthe, Mark Eijgelsheim, Ying A Wang, Kyndaron Reinier, Terho Lehtimäki, Sara L Pulit, Ramon Brugada, Martina Müller-Nurasyid, Chris H Newton-Cheh, Pekka J Karhunen, Bruno H Stricker, Philippe Goyette, Jerome I Rotter, Sumeet S Chugh, Aravinda Chakravarti, Xavier Jouven, David S Siscovick
• Journal: Heart rhythm (Heart Rhythm) Vol. 11 Issue 3 Pg. 471-7 (Mar 2014) ISSN: 1556-3871 [Electronic] United States
• PMID: 24418166 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2014 Heart Rhythm Society. All rights reserved.

Chemical References

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

Topics

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