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

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

Author information

1
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington. Electronic address: rozenl@uw.edu.
2
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
3
Cardiovascular Research Institute and Institute for Human Genetics, University of California, San Francisco, California.
4
Department of Biostatistics, University of Washington, Seattle, Washington.
5
Department of Medicine, University of New Mexico, Albuquerque, New Mexico.
6
Group Health Research Institute, Seattle, Washington.
7
Department of Epidemiology, Harvard University, Boston, Massachusetts; Divisions of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
8
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington; Health Services, University of Washington, Seattle, Washington; Group Health Research Institute, Seattle, Washington.
9
Cedars-Sinai Medical Center, Heart Institute, Los Angeles, California.
10
Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
11
Divisions of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
12
Department of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland.
13
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
14
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University and Munich Heart Alliance, Munich, Germany.
15
Institute of Clinical Medicine, Medical Research Center Oulu, University of Oulu, Oulu, Finland.
16
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging [NCHA], The Netherlands.
17
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
18
Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.
19
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Program in Medical and Population Genetics, the Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
20
Cardiovascular Genetics Center, Institut Investigació Biomèdica de Girona IDIBGI-Universitat de Girona, Girona, Spain.
21
Department of Medicine I, University Hospital Grosshadern, and Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany; Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
22
Center for Human Genetic Research and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Framingham Heart Study, National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Massachusetts.
23
Department of Forensic Medicine, Fimlab Laboratories and University of Tampere School of Medicine, Tampere, Finland.
24
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Netherlands Consortium for Healthy Aging [NCHA], The Netherlands; Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands; Inspectorate for Health Care, The Hague, The Netherlands.
25
Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute, Torrance, California; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
26
Department of Cardiology, University Paris Descartes, Paris, France; Department of Epidemiology, University Paris Descartes, Paris, France.
27
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington; Department of Epidemiology, University of Washington, Seattle, Washington.

Erratum in

  • Heart Rhythm. 2014 Aug;11(8):1496. Sotoodhenia, Nona [corrected to Sotoodehnia, Nona].

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

PMID:
24418166
PMCID:
PMC3966996
DOI:
10.1016/j.hrthm.2014.01.008
[Indexed for MEDLINE]
Free PMC Article

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