Original Article The apolipoprotein E polymorphism and cardiovascular diseases—an autopsy study Neena Theresa Kumar a, ⁎ , Knut Liestøl b , Else Marit Løberg a , Henrik Mikael Reims c , Sverre-Henning Brorson c , Jan Mæhlen a a Department of Pathology, Oslo University Hospital-Ullevål, Oslo, Norway b Department of Informatics, The Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway c Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway Received 23 September 2011; received in revised form 18 January 2012; accepted 10 February 2012 Abstract Background: Numerous studies have addressed the association between the apolipoprotein E polymorphism and cardiovascular disease, but only a few reports are based on findings at autopsy. In the present retrospective study, we have used autopsy findings from a general hospital population to further investigate this issue. Methods and results: We collected information from 1522 consecutive autopsy reports (886 men, mean age 65.7 years; 636 women, mean age 69.7 years) conducted at Oslo University Hospital, Norway, in the period from 1996 to 2000. Cause of death and signs related to cardiovascular disease including the degree of atherosclerosis in the aorta and the coronary arteries, signs of myocardial infarction, heart weight, and signs of cerebrovascular disease were recorded. The patients were genotyped, and the apolipoprotein E allele frequencies (ɛ2, 8.0%; ɛ3, 72.6%; and ɛ4, 19.4%) were not statistically different from a group of healthy controls. Approximately 35% of the patients died from a cardiovascular disease. Genotypes differed significantly (Pb.05), with more ɛ4-carriers (34.3% vs. 29.6%) and fewer ɛ2-carriers (11.8% vs. 13.9%) among patients who died from cardiovascular disease compared to those who died from other causes. A similar distribution of genotypes was seen in patients recorded with myocardial infarction or cerebrovascular disease. There was an association between the presence of ɛ4 and atherosclerosis in the aorta and coronary arteries, but this did not reach statistical significance. Among patients with signs of coronary heart disease, standardized heart weights were significantly higher in ɛ2-carriers compared to ɛ4-carriers. Conclusion: The present autopsy study suggests that the risk of developing and dying from cardiovascular disease, including coronary heart disease and cerebrovascular disease, is influenced by the apolipoprotein E polymorphism. © 2012 Elsevier Inc. All rights reserved. Keywords: Apolipoprotein E; Cardiovascular disease; Atherosclerosis; Autopsy 1. Introduction Cardiovascular disease (CVD), including coronary heart disease (CHD), is still the leading cause of death in Western countries [1]. The pathogenesis is likely to involve a complex interaction among environmental factors, lifestyle, and genetics. Since the early report [2] of lipoprotein(a) as an inheritable factor in the development of CVD, numerous studies, including recent large genomewide association studies, have addressed the genetic basis of CHD and its risk factors [3–5]. During the last decades, the contribution of the apolipoprotein E (apoE) gene polymorphism has been widely discussed [6–13]. ApoE was first described as a protein component of very low density lipoprotein by Shore and Shore in 1973 [14], and in 1977, Utermann et al. [15] discovered that the apoE polymorphism had effects on dysbetalipoproteinemia. The apoE gene is located at chromosome 19q13.2 and is polymorphic with three common alleles designated ɛ2, ɛ3, and ɛ4. The three protein isoforms encoded by these alleles are called E2, E3, and E4, respectively, and are synthesized and secreted mainly in the liver [10]. ApoE plays a part in the lipoprotein metabolism, ultimately altering circulating levels of cholesterol [16]; the ɛ4-allele is associated with increased Cardiovascular Pathology 21 (2012) 461 – 469 This work was supported by the Department of Pathology, Oslo University Hospital, Oslo, Norway, and The Research Council of Norway (Norges forskningsråd). ⁎ Corresponding author. Department of Pathology, Oslo University Hospital-Ullevål, P.O. Box 4956, Nydalen, 0424 Oslo, Norway. Tel.: +47 22 11 89 10, +47 22 11 89 13; fax: +47 22 11 82 39. E-mail address: n.t.kumar@medisin.uio.no (N.T. Kumar). 1054-8807/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2012.02.005