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Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.
Tuesday,2014-04-15 14:58 America/Los_Angeles — poolea2
| Title | Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Lemaitre, 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 |
| Journal | Heart Rhythm |
| Volume | 11 |
| Issue | 3 |
| Pagination | 471-7 |
| Date Published | 2014 Mar |
| ISSN | 1556-3871 |
| Keywords | 1-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 | <p><b>BACKGROUND: </b>There is limited information on genetic factors associated with sudden cardiac arrest (SCA).</p><p><b>OBJECTIVE: </b>To assess the association of common variation in genes in fatty acid pathways with SCA risk.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1016/j.hrthm.2014.01.008 |
| Alternate Journal | Heart Rhythm |
| PubMed ID | 24418166 |
| PubMed Central ID | PMC3966996 |
| Grant List | UL1RR025005 / 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 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 |