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Association analysis of allelic variants of USF1 in coronary atherosclerosis.

ABSTRACT: USF1 regulates the transcription of more than 40 cardiovascular related genes and is well established as a gene associated with familial combined hyperlipidemia, a condition increasing the risk for coronary heart disease. No detailed data, however, exists on the impact of this gene to the critical outcome at the tissue level: different types of atherosclerotic lesions.We analyzed the USF1 in 2 autopsy series of altogether 700 middle-aged men (the Helsinki Sudden Death Study) with quantitative morphometric measurements of coronary atherosclerosis. SNP rs2516839, tagging common USF1 haplotypes, associated with the presence of several types of atherosclerotic lesions, particularly with the proportion of advanced atherosclerotic plaques (P=0.02) and area of calcified lesions (P<0.001) of the coronary arteries. Importantly, carriers of risk alleles of rs2516839 also showed a 2-fold risk for sudden cardiac death (genotype TT versus CC; OR 2.10, 95% CI 1.17 to 3.75, P=0.04). The risk effect of rs2516839 was present also in aorta samples of the men.Our findings in this unique study sample suggest that USF1 contributes to atherosclerosis, the pathological arterial wall phenotype resulting in coronary heart disease and in its most dramatic consequence-sudden cardiac death.

SUBMITTER: Kristiansson K

PROVIDER: S-EPMC2687549 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Association analysis of allelic variants of USF1 in coronary atherosclerosis.

Kristiansson Kati K Ilveskoski Erkki E Lehtimäki Terho T Peltonen Leena L Perola Markus M Karhunen Pekka J PJ

Arteriosclerosis, thrombosis, and vascular biology 20080214 5

<h4>Objective</h4>USF1 regulates the transcription of more than 40 cardiovascular related genes and is well established as a gene associated with familial combined hyperlipidemia, a condition increasing the risk for coronary heart disease. No detailed data, however, exists on the impact of this gene to the critical outcome at the tissue level: different types of atherosclerotic lesions.<h4>Methods and results</h4>We analyzed the USF1 in 2 autopsy series of altogether 700 middle-aged men (the Hel ...[more]

PMID: 18276913

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Project description:BACKGROUND AND AIMS:The impact of tobacco use and cessation on atherogenesis remains unclear. We aimed to study the association of tobacco use and prior cessation with the presence, extent and severity of atherosclerosis on coronary computed tomographic angiography (CTA). METHODS:We examined 1798 consecutive symptomatic patients without known coronary artery disease (CAD) referred for CTA, stratified by smoking status (never, current [within 30 days], or former [>30 days before CTA]). Plaque severity (none, <50%, ?50% stenosis), composition (non-calcified [NCP], partially calcified [PCP], or calcified plaque [CP]), and segment involvement score (SIS) were visually graded. Multivariate analysis was performed, adjusting for CAD risk factors and cholesterol lowering medication use. RESULTS:The median age of patients was 50 years [IQR:42-58] (61% male), with 74% never smokers, 12% current smokers, and 14% former smokers (median quit duration = 12 years [IQR:3-26]). Smoking exposure in former versus current smokers was 11 [IQR:5-25] and 10 [IQR:2-20] pack-years, respectively (p = 0.01). Compared to never smokers, current smokers demonstrated an increased odds ratio of all plaque types (adjusted OR: any NCP = 1.55 [95% CI 1.04-2.32], p = 0.03; any PCP = 1.61 [1.10-2.37], p = 0.02; any CP = 1.93 [1.32-2.81], p = 0.001), non-obstructive CAD (aOR = 1.47 [1.04, 2.07], p = 0.03), obstructive CAD (aOR = 1.81 [1.01-3.24], p = 0.047), and SIS > 4 (aOR = 1.60 [1.04-2.46], p = 0.03). Compared to current smoking, prior smoking cessation (?12 years) was associated with a decreased odds ratio of any NCP (aOR = 0.42 [0.19-0.90], p = 0.03), CP (aOR = 0.43 [0.22-0.84], p = 0.02), and obstructive CAD (aOR = 0.40, [0.15-0.98], p = 0.048). CONCLUSIONS:Current smoking is independently associated with the presence and extent of coronary plaque, and a higher risk of non-obstructive and obstructive CAD compared to never smoking. Prior smoking cessation correlated with improvements in CTA-identified plaque measures.

Dataset Information

Association analysis of allelic variants of USF1 in coronary atherosclerosis.

Publications

Association analysis of allelic variants of USF1 in coronary atherosclerosis.

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