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Genetic Variants from Lipid-Related Pathways and Risk for Incident Myocardial Infarction
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- Song, Ci (author)
- Karolinska Institutet
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- Pedersen, Nancy L. (author)
- Karolinska Institutet
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Reynolds, Chandra A. (author)
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- Sabater-Lleal, Maria (author)
- Karolinska Institutet
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Kanoni, Stavroula (author)
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Willenborg, Christina (author)
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin
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Watkins, Hugh (author)
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- Hamsten, Anders (author)
- Karolinska Institutet
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- Prince, Jonathan A. (author)
- Karolinska Institutet
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- Ingelsson, Erik (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2013-03-29
- 2013
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3, s. e60454-
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https://doi.org/10.1...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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Song, Ci
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Pedersen, Nancy ...
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Reynolds, Chandr ...
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Sabater-Lleal, M ...
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Kanoni, Stavroul ...
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Willenborg, Chri ...
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Syvänen, Ann-Chr ...
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Watkins, Hugh
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Hamsten, Anders
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Prince, Jonathan ...
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Ingelsson, Erik
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Karolinska Institutet