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Heart Rhythm DOI:10.1016/j.hrthm.2014.01.008

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

Publication TypeJournal Article
Year of Publication2014
AuthorsLemaitre, RN, Johnson, CO, Hesselson, S, Sotoodehnia, N, Sotoodhenia, N, McKnight, B, Sitlani, CM, Rea, TD, King, IB, Kwok, P-Y, Mak, A, Li, G, Brody, J, Larson, E, Mozaffarian, D, Psaty, BM, Huertas-Vazquez, A, Tardif, J-C, Albert, CM, Lyytikäinen, L-P, Arking, DE, Kääb, S, Huikuri, HV, Krijthe, BP, Eijgelsheim, M, Wang, YA, Reinier, K, Lehtimäki, T, Pulit, SL, Brugada, R, Müller-Nurasyid, M, Newton-Cheh, CH, Karhunen, PJ, Stricker, BH, Goyette, P, Rotter, JI, Chugh, SS, Chakravarti, A, Jouven, X, Siscovick, DS
JournalHeart Rhythm
Volume11
Issue3
Pages471-7
Date Published2014 Mar
ISSN1556-3871
Keywords1-Acylglycerophosphocholine O-Acyltransferase, Aged, Algorithms, Alleles, Case-Control Studies, Death, Sudden, Cardiac, Fatty Acids, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors
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="" replication="" studies="" totaling="" sca="" cases="" and="" 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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1547-5271(14)00010-1
DOI10.1016/j.hrthm.2014.01.008
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24418166?dopt=Abstract

Alternate JournalHeart Rhythm
PubMed ID24418166
PubMed Central IDPMC3966996
Grant ListUL1RR025005 / RR / NCRR NIH HHS / United States
CA-34944 / CA / NCI NIH HHS / United States
UL1RR033176 / RR / NCRR NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
HL-34595 / HL / NHLBI NIH HHS / United States
HL-46959 / HL / NHLBI NIH HHS / United States
HL-092111 / HL / NHLBI NIH HHS / United States
HL-26490 / HL / NHLBI NIH HHS / United States
N01-HC-85085 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
R01 HL105170-01 / HL / NHLBI NIH HHS / United States
CA 97193 / CA / NCI NIH HHS / United States
N02‐HL‐6‐4278 / HL / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01-HL092111 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
AG-15928 / AG / NIA NIH HHS / United States
R01-HL088456 / HL / NHLBI NIH HHS / United States
R01 HL088416 / HL / NHLBI NIH HHS / United States
CA-87969 / CA / NCI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
R01 HL091244 / HL / NHLBI NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
CA55075 / CA / NCI NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL-34594 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
R01 HL088456 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
K23 DK65978 / DK / NIDDK NIH HHS / United States
CA 40360 / CA / NCI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
R01 HL088416-03S1 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HL-080467 / HL / NHLBI NIH HHS / United States
N01‐HC‐25195 / HC / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
T32 AR007175 / AR / NIAMS NIH HHS / United States
HL-35464 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 HL092144 / HL / NHLBI NIH HHS / United States
R01 HL091069 / HL / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
HL-068070 / HL / NHLBI NIH HHS / United States
R01 HL092111 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States