LIPID PROFILE AND RISK OF MYOCARDIAL INFARCTION IN YOUNG MEN CARRIERS OF DIFFERENT GENOTYPES OF THE APOLIPOPROTEIN AV GENE

Lipid abnormalities, particularly hypertriglyceridemia, are risk factors for coronary heart disease (CHD) and myocardial infarction (MI). Carriage of certain genotypes of the apolipoprotein AV gene is associated with different levels of triglycerides (TG). The data of studies on the relationship S19W polymorphism of the apolipoprotein AV gene with an increased risk of myocardial infarction (MI) are contradictory. In this regard, in this study occurrence of S and W alleles and distribution S19S, S19W and W19W apolipoprotein AV gene genotypes in patients with CHD, after MI at different age, and in healthy men, residents of St. Petersburg, was analyzed. The study included 406 men, residents of St. Petersburg. The first group consisted of 194 patients after MI under the age of 45 years, mean age 44,3 ± 0,4 years old. The second group included 95 men aged 60 to 84 years (mean age 71,5 ± 0,6 years old), in which MI developed over the age of 60. The third group consisted of 117 apparently healthy men of comparable age from the first group (42,7 ± 0,4 and 44,3 ± 0,4 y.o., respectively; p > 0,05). All the men were determined with lipid profile of blood serum and identified with S19W polymorphism apo AV gene. In patients after MI under age of 45 years, the levels of TC, TG and VLDL were significantly higher, and the value of HDL-C was significantly lower compared with those in healthy men and in patients after MI over the age of 60 years. Among MI patients under age of 45 years were significantly more carriers of S19W genotype than among healthy men (p < 0,05, OR = 5,4 (1,58 ÷ 18,23). Carriage of S19W apolipoprotein AV genotype is associated with increased risk of myocardial infarction in young men. Lipid profile of blood serum do not differ in men with myocardial infarction - S19S carriers and S19W genotype apolipoprotein AV gene.

метаболизм липидов, инфаркт миокарда, аполипопротеин АV, S19W полиморфизм, полиморфизм генов, Lipid metabolism, myocardial infarction, apolipoprotein AV, S19W polymorphism

1. Hokanson J.E., Austin M.A. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of populationbased prospective studies // J. Cardiovasc. Risk. -1996. - № 3. - P. 213-219.

2. Cullen P. Evidence that triglycerides are an independent coronary heart disease risk factor // Am. J. Cardiol. - 2000. - № 86. - P. 943-949.

3. Forrester J.S. Triglycerides: risk factor or fellow traveler? // Curr. Opin. Cardiol. - 2001. - № 16. - P. 261-264.

4. Wang Q. Molecular genetics of coronary artery disease // Curr. Opin. Cardiol. - 2005. - № 20. - P. 182-188.

5. Chandak G.R., Ward K.J., Yajnik C.S. et al. Triglyce-ride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India, compared to Europeans // BMC Med. Genet. - 2006. - № 7. - P. 76.

6. Hamon S.C., Kardia S.L., Boerwinkle E. et al. Evidence for consistent intragenic and intergenic interactions between SNP effects in the ApoAI/CIII/AIV/AV gene cluster // Hum. Hered. - 2006. - Vol. 61, № 2. - P. 87-96.

7. Karathanasis S. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes // Proc. Natl. Acad. Sci. USA. - 1985. - Vol. 82, № 19. - P. 6374-6378.

8. Groenendijk M., Cantor R.M., Funke H. et al. Two newly identified SNPs in the APO AI-CIII intergenic region are strongly associated with familial combined hyperlipidaemia // Eur. J. Clin. Invest. - 2001. - Vol. 31, № 10. - P. 852-859.

9. Delgado-Lista J., Perez-Jimenez F., Ruano J. et al. Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men // J. Lipid. Res. - 2010. - Vol. 51, № 1. - P. 63-73.

10. Pennacchio L.A., Olivier M., Hubacek J.A. et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing // Science. - 2001. - Vol. 294, № 5540. - P. 169-173.

11. Pennacchio L.A., Olivier M., Hubacek J.A. et al. Two independent apolipoprotein AV haplotypes influence human plasma triglyceride levels // Hum. Mol. Genet. - 2002. - Vol. 11, № 24. - P. 3031-3038.

12. Henneman P., Schaap F.G., Havekes L.M. et al. Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism // Atherosclerosis. - 2007. - Vol. 193, № 1. - P. 129-134.

13. Lai C.Q., Demissie S., Cupples L.A. et al. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study // J. Lipid Res. - 2004. - Vol. 45. - P. 2096-2105.

14. Talmud P.J., Martin S., Taskinen M.-R. Apo AV gene variants, lipoprotein particle distribution, and progression coronary heart disease: results from the LOCAT study // J. Lip. Res. - 2004. - Vol. 45. - P. 750-756.

15. Ding Y., Zhu M.A., Wang Z.X. et al. Associations of polymorphisms in the apolipoprotein APOA1-C3-A5 gene cluster with acute coronary syndrome // Biomed. Biotech-nol. - 2012. - 509420.

16. Hubacek J.A., Skodova Z., Adamkova V. et al. The influence of APOAV polymorphisms (T-1131 > C and S19 > W) on plasma triglyceride levels and risk of myocardial infarction // Clin. Genet. - 2004. - Vol. 65. - P. 126-130.

17. Dallongeville J., Cottel D., Montaye M. et al. Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men // Int. J. Cardiol. - 2006. - Vol. 106. - P. 152-156.

18. Martinelli N., Trabetti E., Bassi A. et al. The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study // Atherosclerosis. - 2007. - Vol. 191. - P. 409-417.

19. Prochaska C.L., Picheth G., Anghebem-Oliveira M.I. The polymorphisms -1131T>C and the S19W of the APOA5 gene are not associated with coronary artery disease in a Brazilian population // Clin. Chem. Lab. Med. - 2010. - Vol. 48. - P. 419-422.

20. Климов А.Н., Ганелина И.Е. Фенотипирование гиперлипидемий // М.: Медицина, 1975. - C. 47.

21. Friedewald W.T., Levy R.I., Fredrickson D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge // Clin. Chem. - 1972. - Vol. 18, № 6. - P. 499-502.

22. Kunkel L.M., Smith K.D., Boyer S.H. et al. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants // Proc. Natl. Acad. Sci. USA. - 1977. - Vol. 74, № 3. - P. 1245-1249.

23. Lahiri D.K., Bye S., Nurberger J.I. et al. A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested // J. Biochem. Biophys. Methods. - 1992. - Vol. 25, № 4. - P. 193-205.

24. Talmud P.J., Hawe E., Martin S. et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides // Hum. Mol. Genet. - 2002. - Vol. 11, № 24. - P. 3039-3046.

25. Zhang Z., Peng B., Gong R. et al. Apolipoprotein A5 polymorphisms and risk of coronary artery disease: a meta-analysis // BioScience Trends. - 2011. - Vol. 5, № 4. - P. 165-172.

26. Guardiola M., Ribalta J., Gómez-Coronado D. et al. The apolipoprotein A5 (APOA5) gene predisposes Caucasian children to elevated triglycerides and vitamin E (Four Provinces Study) // Atherosclerosis. - 2010. - Vol. 212, № 2. - P. 543-547.

27. Evans D., Bode A., von der Lippe G. et al. Cerebrovascular atherosclerosis in type III hyperlipidemia is modulated by variation In the apolipoprotein A5 gene // Eur. J. Med. Res. - 2011. - Vol. 16. - P. 79-84.

28. Perez-Martinez P., Corella D., Shen J. et al. Associaton between glukinase protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states // Am. J. Clin. Nutr. - 2009. - Vol. 89. - P. 391399.

29. Sóter M.O., Gomes K.B., Fernandes A.P. et al. -1131T > C and SW19 polymorphisms in APOA5 gene and lipid levels in type 2 diabetic patients // Mol. Biol. Rep. - 2012. - Vol. 39, № 7. - P. 7541-7548.

30. Gesteiro E., Bastida S., Vázquez-Velasco M. et al. Effects of APOA5 S19W polymorphism on growth, insulin sensitivity and lipoproteins in normoweight neonates // Eur. J. Pediatr. - 2011. - Vol. 170, № 12. - P. 1551-1558.