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Song, C.* ; Pedersen, N.L.* ; Reynolds, C.A.* ; Sabater-Lleal, M.* ; Kanoni, S.* ; Willenborg, C.* ; CARDIoGRAMplusC4D Consortium (Gieger, C. ; Meitinger, T. ; Peters, A.) ; Syvanen, A.C.* ; Watkins, H.* ; Hamsten, A.* ; Prince, J.A.* ; Ingelsson, E.*

Genetic variants from lipid-related pathways and risk for incident myocardial infarction.

PLoS ONE 8:e60454 (2013)
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Background: Circulating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI). Objectives: We hypothesized that genetic variants associated with circulating lipid levels would also be associated with MI incidence, and have tested this in three independent samples. Setting and Subjects: Using age- and sex-adjusted additive genetic models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate gene regions proposed to be involved in lipid-related pathways potentially predisposing to incidence of MI in 2,602 participants of the Swedish Twin Register (STR; 57% women). All associations with nominal P<0.01 were further investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142). Results: In the present study, we report associations of lipid-related SNPs with incident MI in two community-based longitudinal studies with in silico replication in a meta-analysis of genome-wide association studies. Overall, there were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both longitudinal study samples with nominal significance (hazard ratio, 1.36 and 1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico replication supported the association of rs4149313 with coronary artery disease in an independent meta-analysis including 173,975 individuals of European descent from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048). Conclusions: rs4149313 is one of the few amino acid changing variants in ABCA1 known to associate with reduced cholesterol efflux. Our results are suggestive of a weak association between this variant and the development of atherosclerosis and MI.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Coronary-Heart-Disease; Swedish Twin Registry; Association; Population; Cholesterol; Dementia; Health; Loci
Language german
Publication Year 2013
HGF-reported in Year 0
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 8, Issue: 3, Pages: , Article Number: e60454 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504091-004
G-500700-001
G-504000-002
DOI 10.1371/journal.pone.0060454
WOS ID WOS:000317263900073
Erfassungsdatum 2013-12-31
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