Influence of the SstI Polymorphism in the Apolipoprotein C3 Gene on the Dyslipidemia and Coronary Lesions in Patients with Unstable Angina

A.S. Eshpulatov; S.U. Hashimov; F.M. Bekmetova, PhD; A.B. Shek, PhD, ScD; R.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

Abstract: 

The aim of our study was to evaluate the distribution of the APOC3 SstI polymorphism and its impact on the character of dyslipidemia and features of coronary lesions in Uzbek patients with unstable angina.

Material and Methods: The study included 141 patients with unstable angina (UA) class IIB (Braunwald E. et al., 1989) having LDL-C>100mg/dL. The comparison group included 50 healthy, age-matched, randomly selected 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 APOC3 SstI  gene polymorphism was performed by PCR-RFLP method. The alleles lacking the restriction site were designated as S1, while those containing the SstI site were designated as S2.

Results: Performed analysis of APOC3 SstI polymorphism revealed a significant prevalence of S2 allele carriers among UA patients compared to healthy ethnic Uzbeks. Being a carrier of S2 allele was associated with hypertriglyceridemia (> 230 mg / dL) (OR= 2.30, 95% CI: 1.14-4.67; χ²=5.485; Р=0.02) and higher risk of having three- and multi-vessel lesions (OR=2.171, 95% CI: 1.0792-4.3680; Р=0.03).

Conclusion: Our results suggest that the definition of APOC3 SstI polymorphism may be a useful additional marker in the evaluation of heart-vascular risk and indications for coronary angiography.

Keywords: 
APOC3 SstI gene polymorphism; hypertriglyceridemia; unstable angina; coronary artery lesions.
References: 
  1. Couillard C, Vohl MC, Engert JC, Lemieux I, Houde A, Almeras N, et al. Effect of apoC-III gene polymorphisms on the lipoprotein-lipid profile of viscerally obese men. J Lipid Res 2003; 44(5):986-93.
  2. Talmud PJ, Humphries SE. Apolipoprotein C–III gene variation and dyslipidaemia. Curr Opin Lipidol 1997; 8:154–8.
  3. Rees A, Shoulders CC, Stocks J, Galton DJ, Baralle FE. DNA polymorphism adjacent to human apoprotein A-1 gene: relation to hypertriglyceridaemia. Lancet 1983; 1:444–6.
  4.  Salas  J,  Jansen S, Lopez-Miranda J,  Ordovas JM, Castro P, Marin C,  et al. The SstI polymorphism of the apolipoprotein C–III gene determines the insulin response to an oral-glucose-tolerance test after consumption of a diet rich in saturated fats. Am J Clin Nutr 1998; 68(2):396–401.
  5. Tybjaerg-Hansen A, Nordestgaard BG, Gerdes LU, Faergeman O,  Humphries SE.  Genetic markers in the apo AI-C-IIIAIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosis. Atherosclerosis 1993; 100(2):157–69.
  6. Ordovas JM, Civeira F,  Genest JJr, Craig S, Robbins AH, Meade T,  et al. Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature
  7. coronary artery disease. Atherosclerosis 1991; 87(1):75–86.
  8. Hoffer MJ, Sijbrands EJ, De Man FH, Havekes LM, Smelt AH, Frants RR. Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism. Eur J Clin Invest 1998; 28:807–12.
  9. Zeng Q, Dammerman M, Takada Y, Matsunaga A, Breslow JL, Sasaki J. An apolipoprotein CIII marker associated with hypertriglyceridemia in Caucasians also confers increased risk in a west Japanese population. Hum Genet 1995; 95(4):371–5.
  10. Wang CS, McConathy WJ, Kloer HU, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest 1985; 75(2):384-90.
  11.  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(16):1886-92.
  12. 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.
  13. Tsai MY, Ordovas JM. APOC3 mutation, serum triglyceride concentrations, and coronary heart disease. Clin Chem 2009; 55(7):1274-6.
  14. Olivieri O, Bassi A, Stranieri C, Trabetti E, Martinelli N, Pizzolo F, et al. Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. J Lipid Res 2003; 44(12):2374-81.
  15. Campos H, Perlov D, Khoo C, Sacks FM. Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia. J Lipid Res 2001; 42:1239-49.
  16.  Johansen CT, Kathiresan S, Hegele RA. Genetic determinants of plasma triglycerides. J Lipid Res 2011; 52(2):189–206.
  17. Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL. Hypertriglyceridemia as a result of human apoCIII gene expression in transgenic mice. Science 1990; 249(4970):790–3.

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IJBM 2014; 4(4) Suppl 1:S15-S19. © 2014 International Medical Research and Development Corporation. All rights reserved.