Age-dependent association of apolipoprotein e genotype with coronary and aortic atherosclerosis in middle-aged men: An autopsy study

Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE epsilon4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel...

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Published in:	Circulation (New York, N.Y.) Vol. 100; no. 6; pp. 608 - 613
Main Authors:	ILVESKOSKI, E, PEROLA, M, KOIVULA, T, KARHUNEN, P. J, LEHTIMÄKI, T, LAIPPALA, P, SAVOLAINEN, V, PAJARINEN, J, PENTTILÄ, A, LALU, K. H, MÄNNIKKÖ, A, LIESTO, K. K
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 10-08-1999 American Heart Association, Inc
Subjects:	Age Factors Alcoholism - mortality Alleles Aorta, Abdominal - pathology Aorta, Thoracic - pathology Aortic Diseases - epidemiology Apolipoprotein E3 Apolipoprotein E4 Apolipoproteins E - genetics Arteriosclerosis - epidemiology Arteriosclerosis - genetics Arteriosclerosis - pathology Atherosclerosis (general aspects, experimental research) Autopsy Biological and medical sciences Blood and lymphatic vessels Body Mass Index Cardiology. Vascular system Cardiovascular Diseases - mortality Cause of Death Comorbidity Coronary Artery Disease - epidemiology Coronary Artery Disease - genetics Coronary Artery Disease - pathology Finland - epidemiology Gene Frequency Genetic Predisposition to Disease Genotype Heterozygote Humans Male Medical sciences Middle Aged Obesity - epidemiology Violence Finland Human Pathogenesis Coronary artery Cardiovascular disease Exploration Genotype Coronary heart disease Genetic determinism Vascular disease Gene Apolipoprotein E Autopsy Atherosclerosis Risk factor Aorta Aortic disease
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Summary:	Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE epsilon4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel-wall level, nor is any age-dependent effect of the apoE genotype on the development of CHD known. The right and left anterior descending coronary arteries (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, fibrotic plaques, and complicated lesions were measured. In the RCA and LAD, the apoE genotype was significantly associated with the area of total atherosclerotic lesions in men <53 years old but not with that in older men (P=0.0085 and P=0.041, respectively, for age-by-genotype interaction). Men <53 years old with the epsilon4/3 genotype showed 61% larger total atherosclerotic lesion area in the RCA (P=0.0027) and 26% larger area in the LAD (P=0.12) than did men with the epsilon3/3. The apoE epsilon4/3 was also associated with atherosclerotic lesions in the abdominal (P=0.014) and thoracic (P=0.12) aorta, but this effect, unlike that of the coronary arteries, was not age-related. In men, the apoE epsilon4 allele is a significant genetic risk factor for coronary atherosclerosis in early middle age. This suggests that at older age, other known risk factors of CHD play a more important role in the atherosclerotic process than apoE polymorphisms.
ISSN:	0009-7322 1524-4539
DOI:	10.1161/01.CIR.100.6.608