Apolipoprotein E Gene Polymorphism in Iranian Coronary Atherosclerosis Patients Candidate for Coronary Artery Bypass Graft

Document Type : Original Article


1 Department of Biology, Science School, Yazd University, Yazd, Iran

2 Department of Cardiac Surgery, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran



Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary artery disease (CAD) risk. The aim of this study was to study the association of the Apolipoprotein E genotypes with coronary artery disease in the Iranian population.
Materials and Methods:
The Apolipoprotein E genotype in DNA samples extracted from 66 CAD+ patients and 61 control subjects by restricting enzyme digestion of amplified exon 4 APOE gene was determined.
: The ε3 allele was found at similar frequency in control subjects (88.5%) and atherosclerosis patients (83.3%) (P=0.314). Our results showed that the frequency of the ɛ3/ɛ3 and ε3/ε4 genotypes increased in three-vessel-disease patients and the frequency of ɛ2/ɛ2 genotype increased in one-vessel-disease patients.
: ɛ3/ɛ3 and ɛ3/ɛ4 genotypes are suggested to be predisposing factors, which, in combination with environmental factors, may trigger the degree of luminal narrowing. The possible mechanisms remain elusive and require further studies.


1. Relationship of atherosclerosis in young men to serum lipoprotein cholesterol concentrations and smoking. A preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990; 264:3018-0324.
2. Ghayour-Mobarhan M , Starkey B, Livingstone C, Wang T, Lamb D, Ferns G. An investigation of the relationship between serum vitamin E status and coronary risk factors in dyslipidaemic patients. Iran J Basic Med Sci 2008; 4:206 - 215.
3. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988; 240:622-630.
4. Walden CC, Hegele RA. Apolipoprotein E in hyperlipidemia. Ann Inter Med 1994; 120:1026-1036.
5. Das HK, McPherson J, Bruns GA, Karathanasis SK, Breslow JL. Isolation, characterization, and mapping to chromosome 19 of the human apolipoprotein E gene. J Biol Chem 1985; 260:6240-6247.
6. Paik YK, Chang DJ, Reardon CA, Davies GE, Mahley RW, Taylor JM. Nucleotide sequence and structure of the human apolipoprotein E gene. Proc Nat Acad Sci U S A 1985; 82:3445-3449.
7. Smith JD, Melian A, Leff T, Breslow JL. Expression of the human apolipoprotein E gene is regulated by multiple positive and negative elements. J Biol Chem 1988; 263:8300-8308.
8. MO MC, Muir KW, Weir CJ, Dyker AG, Bone I, Nicoll JA, et al. The apolipoprotein E epsilon4 allele and outcome in cerebrovascular disease. Stroke 1998; 29:1882-1887.
9. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 1997; 278:1349-1356.
10. Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990; 31:545-548.
11. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988; 8:1-21.
12. Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, et al. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 2007; 298:1300-1311.
13. Anuurad E, Rubin J, Lu G, Pearson TA, Holleran S, Ramakrishnan R, et al. Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol. J Lipid Res 2006; 47:2475-2481.
14. Wilson PWF, D'Agostino R, Levy D, Belanger AM, Silbershatz H. Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837-1847.
15. Ferreira CN, Carvalho MG, Fernandes AP, Lima LM, Loures-Valle AA, Dantas J, et al. Comparative study of apolipoprotein-E polymorphism and plasma lipid levels in dyslipidemic and asymptomatic subjects, and their implication in cardio/cerebro-vascular disorders. Neurochem Int 2010; 56:177-182.
16. Topic A, Spasojevic Kalimanovska V, Zeljkovic A, Vekic J, Jelic Ivanovic Z. Gender-related effect of apo E polymorphism on lipoprotein particle sizes in the middle-aged subjects. Clin Biochem 2008; 41:361-367.
17. Akanji AO, Suresh CG, Fatania HR, Al-Radwan R, Zubaid M. Associations of apolipoprotein E polymorphism with low-density lipoprotein size and subfraction profiles in Arab patients with coronary heart disease. Metabolism 2007; 56:484-490.
18. Mahley RW, Palaoglu KE, Atak Z, Dawson-Pepin J, Langlois AM, Cheung V, et al. Turkish Heart Study: lipids, lipoproteins, and apolipoproteins. J Lipid Res 1995; 36:839-859.
19. Rask-Nissila L, Jokinen E, Viikari J, Tammi A, Ronnemaa T, Marniemi J, et al. Impact of dietary intervention, sex, and apolipoprotein E phenotype on tracking of serum lipids and apolipoproteins in 1- to 5-year-old children: the Special Turku Coronary Risk Factor Intervention Project (STRIP). Arterioscler Thromb Vasc Biol 2002; 22:492-498.
20. Srinivasan SR, Wattigney W, Webber LS, Berenson GS. Serum apolipoprotein E in children and adolescents: the Bogalusa Heart Study. Metabolism 1989; 38:1173-1178.
21. Wang Y, Zhang Y, Dong G. Dong The correlation between APOE gene polymorphisms and carotid artery stenosis. Chin J Gerontol. 2008;16:1615–7.