LIPID TRANSPORT GENETIC POLYMORPHISM AND ANGIOTENSIN-CONVERTING ENZYME I/D GENETIC POLYMORPHISM IN UZBEK PATIENTS WITH UNSTABLE ANGINA AND CORONARY HEART DISEASE IN FAMILY HISTORY

Aim. To study the impact of coronary heart disease (CHD) in family history on the genetic polymorphisms of apolipoprotein (apo) A1, B, and E and angiotensin-converting enzyme (ACE) in Uzbek patients with unstable angina (UA).

Material and methods. The study included 125 Uzbek patients with UA. Group I (n=63) had CHD in family history, Group II (n=62) had no CHD in family history, and the control group included 58 healthy individuals. The following genetic polymorphisms were investigated, using the Diatom TM DNA Prep 200 kit (IsoGen Laboratory Ltd.): apoA1 G-A polymorphism; apoB –516C/T polymorphism; apoE ε2/ε3/ε4 polymorphism, and ACE I/D polymorphism.

Results. In UA patients, compared to healthy controls, the prevalence of apoA1 A allele was significantly higher (odds ratio (OR) 3,63; 95% confidence interval (CI) 1,63–8,04; p=0,002). The distribution of the “damaging” alleles was similar in Group II and the control group, while Group I demonstrated a significantly higher prevalence of A alleles of the apoA1 G-A polymorphism (OR 5,99; 95% CI 2,52–14,24; p=0,001); ε4 allele of the apoE gene (OR 2,91; 95% CI 1,12–7,62; p=0,044); and D allele of the ACE I/D polymorphism (OR 2,88; 95% CI 1,33–6,27; p=0,024). At the same time, there was no marked difference in the distribution of the T allele of the apoB –516C/T polymorphism.

Conclusion. In Uzbek patients with UA, CHD in family history is associated with the higher prevalence of the following “damaging” alleles: A allele (M1-) of the apoA1 G-A polymorphism; ε4 allele of the ApoE gene; and D allele of the ACE I/D polymorphism. There was no significant difference in the distribution of T allele of the apoB –516C/T polymorphism.

unstable angina, angiotensin-converting enzyme genetic polymorphism, coronary heart disease in family history, intima-media thickness

1. Van’t Hooft FM, Jormsjö S, Lundahl B, et al. A functional polymorphism in the apolipoprotein B promoter that influences the level of plasma low density lipoprotein. J Lipid Res 1999; 40: 1686–94.

2. Zou Yangchun, Hu Dayi, Yang Xinchun, et al. Relationships among apolipoprotein A1 gene polymorphisms, lipid levels and coronary atherosclerosis disease. Chinese Medical J 2003; 116: 5: 665–8.

3. Gerdes LU, Jeune B, Ranberg KA, et al. Estimation of apolipoprotein E genotype specific relative mortality from the distribution of genotypes in centenarians and middle-aged men: Apolipoprotein E gene is a «frailty gene», not a «longevity gene» Genetic Epidemiol 2000; 19: 202–10.

4. Jeenah M, Kessling A, Miller N, Humphries SE. G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations. Mol Biol Med 1990; 7: 233–41.

5. Pagani F, Sidoli A, Giudici GA, et al. Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia. J Lipid Res 1990; 31: 1371–7.

6. Civeira F, Pocovi M, Cenarro A, et al. Adenine for guanine substitution –78 base pairs to the apolipoprotein (APO) A-I gene: relation with high-density lipoprotein cholesterol and apoA-I concentrations. Clin Genet 1993; 44: 307–12.

7. Wang XL, Liu SX, McCredie RM, Wilcken DEL. Polymorphisms at the 5‘-end of the apolipoprotein AI gene and severity of coronary artery disease. J Clin Invest 1996; 98: 372–7.

8. Matsunaga A, Sasaki J, Mori T, et al. Apolipoprotein A-I gene promoter polymorphism in patients with coronary artery disease and healthy controls. Nutr Metab Cardiovasc Dis 1995; 5: 269–75.

9. . Ali I Albahrani, Jannete Usher J, Mohammed Alkindi, et al. Apolipoprotein A1–75 G/A (M1-) polymorphism and Lipoprotein (a) Anti- versus Pro-Atherogenic properties. Lipids in Health and Disease 2007; 6: 19.

10. Heng CК, Low PS, Saha N. Variations in the promoter region of the apolipoprotein A-1 gene influence plasma lipoprotein (a) levels in Asian Indian neonates from Singapore. Pediatr Res 2001; 49: 514–8.

11. Requero JR, Cubero GI, Batalla A, et al. Apolipoprotein AI gene polymorphisms and risk of early Coronary disease. Cardiology 1998; 90: 231–5.

12. 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.

13. Gerdes LU, Gerdes C, Kervinen K, 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: 1366–71.

14. Chiodini BD, Franzosi MG, Barlera S, et al. Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study. Eur Heart J 2007; 28: 16: 1977–83.

15. Van Geel PP, Pinto YM, Zwinderman AH, et al. Synergistic effects of angiotensin converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on ischaemic events XX Congress of the European society of Cardiology 2001; Abstract: 386.