Dataset Information

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.

SUBMITTER: Lemaitre RN

PROVIDER: S-EPMC3966996 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Lemaitre Rozenn N RN Johnson Catherine O CO Hesselson Stephanie S Sotoodehnia Nona N McKnight Barbara B Sitlani Colleen M CM Rea Thomas D TD King Irena B IB Kwok Pui-Yan PY Mak Angel A Li Guo G Brody Jennifer J Larson Eric E Mozaffarian Dariush D Psaty Bruce M BM Huertas-Vazquez Adriana A Tardif Jean-Claude JC Albert Christine M CM Lyytikäinen Leo-Pekka LP Arking Dan E DE Kääb Stefan S Huikuri Heikki V HV Krijthe Bouwe P BP Eijgelsheim Mark M Wang Ying A YA Reinier Kyndaron K Lehtimäki Terho T Pulit Sara L SL Brugada Ramon R Müller-Nurasyid Martina M Newton-Cheh Chris H CH Karhunen Pekka J PJ Stricker Bruno H BH Goyette Philippe P Rotter Jerome I JI Chugh Sumeet S SS Chakravarti Aravinda A Jouven Xavier X Siscovick David S DS

Heart rhythm 20140110 3

<h4>Background</h4>There is limited information on genetic factors associated with sudden cardiac arrest (SCA).<h4>Objective</h4>To assess the association of common variation in genes in fatty acid pathways with SCA risk.<h4>Methods</h4>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 gre ...[more]

PMID: 24418166

Similar Datasets

Project description:ObjectiveEthnic differences in sudden cardiac arrest resuscitation have not been fully explored and studies have yielded inconsistent results. We examined the association of ethnicity with factors affecting sudden cardiac arrest outcomes.MethodsRetrospective cohort study of 3551 white, 440 black and 297 Asian sudden cardiac arrest cases in Seattle and King County, Washington, USA.ResultsCompared with whites, blacks and Asians were younger, had lower socioeconomic status and were more likely to have diabetes, hypertension and end-stage renal disease (all p<0.001). Blacks and Asians were less likely to have a witnessed arrest (whites 57.6%, blacks 52.1%, Asians 46.1%, p<0.001) or receive bystander cardiopulmonary resuscitation (whites 50.9%, blacks 41.4%, Asians 47.1%, p=0.001), but had shorter average emergency medical services response time (mean in minutes: whites 5.18, blacks 4.75, Asians 4.85, p<0.001). Compared with whites, blacks were more likely to be found in pulseless electrical activity (blacks 20.9% vs whites 16.6%, p<0.001), and Asians were more likely to be found in asystole (Asians 41.1% vs whites 30.0%, p<0.001). One of the strongest predictors of resuscitation outcomes was initial cardiac rhythm with 25% of ventricular fibrillation, 4% of patients with pulseless electrical activity and 1% of patients with asystole surviving to hospital discharge (adjusted OR of resuscitation in pulseless electrical activity compared with ventricular fibrillation: 0.30, 95% CI 0.24 to 0.34, p<0.001, adjusted OR of resuscitation in asystole relative to ventricular fibrillation 0.21, 95% CI 0.17 to 0.26, p<0.001). Survival to hospital discharge was similar across all three ethnicities.ConclusionsWhile there were differences in some prognostic characteristics between blacks, whites and Asians, we did not detect a significant difference in survival following sudden cardiac arrest between the three ethnic groups. There was, however, an ethnic difference in presenting rhythm, with pulseless electrical activity more prevalent in blacks and asystole more prevalent in Asians.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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