Influence of Lipid Transport System Gene Polymorphism on the Dyslipidemia and Coronary Lesions in Patients with Unstable Angina

ORIGINAL ARTICLE
Aziz S. Eshpulatov; S.U. Hashimov; Alexander B. Shek, PhD, ScD; Ravshanbek D. Kurbanov, PhD, ScD

The Republican Specialized Center of Cardiology; Tashkent, Uzbekistan

*Corresponding author: Aziz S. Eshpulatov.  The Republican Specialized Center of Cardiology; Tashkent, Uzbekistan. E-mail: dr.azizbek84@mail.ru

Published: December 3, 2015. DOI: 10.21103/Article5(4)_OA3

Abstract: 

The purpose of this study was to identify the features of lipid metabolism and coronary lesions in view of the combined carrier of the ε4 allele of APOE ε2/ε3/ε4 polymorphism and the S2 allele of APOC3SstI polymorphism in UA patients.

Materials and Methods: The study included 141 Uzbek patients with UA class IIB (Braunwald E. et al., 1989) who had coronary atherosclerosis of varying degrees, according to coronary angiography. The control group consisted of 50 healthy, age-matched, randomly selected Uzbek persons without clinical and instrumental signs of CHD according to the exercise test. Coronary angiography was performed using Allura CV-20 (Philips, Netherlands). Genotyping of the APOE (ε2/ε3/ε4) gene polymorphism and the APOC3 (SstI) gene polymorphism was performed by the PCR-RFLP method.

Results: Our analysis revealed a significant prevalence of carriers of the S2 allele of APOC3SstI polymorphism and carriers of the ε4 allele of APOE ε2/ε3/ε4 polymorphism among UA patients compared to healthy ethnic Uzbeks. A combination of these two “damaging” alleles was observed in 26.2% of UA patients, which was accompanied by significantly higher blood levels of TC and LDL-C (P<0.05), a higher APOB/APOAI ratio (P<0.05), and a lower level of HDL-C (P<0.05). According to coronary angiography, a three-vessel lesion and more significantly predominated among these UA patients (OR=2.25, 95% CI: 1.05-4.84, χ2 =3.66, p<0.05).

Keywords: 
APOC3 SstI gene polymorphism; APOE (ε2/ε3/ε4) gene polymorphism; unstable angina; Dyslipidemia; Coronary Lesions.
References: 
  1. Vinogradova SV. The role of apolipoprotein E gene polymorphism in the development of atherosclerosis (review). Medical Genetics. 2006; 2:3-10 [Article in Russian].
  2. Song Y. Stampfer MJ. Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Int Med. 2004;141(2):137-47.
  3. Davignon J, Cohn JS, Mabile L, Bernier L. Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta. 1999; 286:115-43.
  4. de Andrade M, Thandi I, Brown S, Gotto A Jr, Patsch W, Boerwinkle E. Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis. Am J Hum Genet. 1995; 56:1379-90.
  5. Wang CS, McConathy WJ, Kloer HU, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins. J Clin Invest. 1985; 75:384-90.
  6. Sacks FM, Alaupovic P, Moye LA, Cole TG, Sussex B, Stampfer MJ, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000;102:1886-92.
  7. Alaupovic P, Mack WJ, Knight-Gibson C, Hodis HN. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial. Arterioscler Thromb Vasc Biol. 1997;17(4):715-22.
  8. Tsai MY, Ordovas JM. APOC3 mutation, serum triglyceride concentrations, and coronary heart disease. Clin Chem. 2009; 55(7):1274-6.
  9. Gerdes LU, Gerdes C, Kervinen K, Savolainen M, Klausen IC, Hansen PS, et al. The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction: a substudy of the Scandinavian simvastatin survival study. Circulation. 2000; 101(12):1366-71.
  10. Bekmetova FM. Kan LE. Hoshimov SU. Kurbanov RD. Clinical value distribution of  polymorphism of  the lipidtransport systems genes in patients with unstable angina and coronary heart disease in family history. Eurasian Heart J. 2013; 2:51-59. [Article in Russian].
  11. Eshpulatov AS, Hashimov SU, Bekmetova FM, Shek AB, Kurbanov RD. Influence of the SstI polymorphism in the apolipoprotein C3 gene on the dyslipidemia and coronary lesions in patients with unstable angina. Int J Biomed. 2014; 4(4, Suppl1):15-9.
  12. Eshpulatov AS, Hashimov SU, Bekmetova FM, Shek AB, Kurbanov RD. Distribution of gene APO CIII polymorphism in unstable angina patients with three-vessel coronary arteries lesion. Kardioangiologia i Revmatologia. 2014; 7:23-29. [Article in Russian].
  13. Bandegi AR, Firoozrai M, Akbari Eidgahi MR, Kokhaei P. SstI Polymorphism of the Apolipoprotein CIII Gene in Iranian Hyperlipidemic Patients: A Study in Semnan Province. Iran J Basic Med Sci. 2011;14(6):506-13.
  14. Wenham PR, Price WH, Blundell G. Apolipoprotein E genotyping by one-stage PCR. Lancet.1991;337(8750):1158–9.
  15. Eichner JE, Kuller LH, Orchard TJ, Grandits GA, McCallum LM, Ferrell RE, et al. Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. Am J Cardiol. 1993;71(2):160-5.
  16. Lehtinen S, Lehtimaki T, Sisto T, Salenius JP, Nikkila M, Jokela H, et al. Apolipoprotein E polymorphism, serum lipids, myocardial infarction and severity of angiographically verified coronary artery disease in men and women. Atherosclerosis. 1995;114(1):83–91.
  17. Utermann G. Apolipoprotein Epolymorphism in health and disease. Am Heart J. 1987;113(2 Pt 2):433–40.
  18. Schiele F, De Bacquer D, Vincent-Viry M, Beisiegel U, Enholm C, Evans A, et al. Apolipoprotein E serum concentration and polymorphism in six European countries: the ApoEurope Project. Atherosclerosis. 2000;152(2):475–88.
  19. Hixson JE. Apolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb. 1991;11(5):1237–44.
  20. Ilveskoski E, Perola M, Lehtimaki T, Laippala P, Savolainen V, Pajarinen J, et al. Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men: an autopsy study. Circulation. 1999;100(6):608–13.
  21. Lima LM, Carvalho Md, Ferreira CN, Fernandes AP, Neto CP, Garcia JC, et al. Atheromatosis extent in coronary artery disease is not correlated with apolipoprotein-E polymorphism and its plasma levels, but associated with cognitive decline. Curr Alzheimer Res. 2010;7(6):556–63.
  22. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol. 1988;41(2):105–14.
  23. Lahoz C, Schaefer EJ, Cupples LA, Wilson PW, Levy D, Osgood D, et al. Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study. Atherosclerosis. 2001;154(3):529–37.
  24. Russo GT, Meigs JB, Cupples LA, Demissie S, Otvos JD, Wilson PW, et al. Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study. Atherosclerosis. 2001; 158(1):173-81.

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Int J Biomed. 2015; 5(4):188-191. © 2015 International Medical Research and Development Corporation. All rights reserved.