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Factors determining homocysteine levels in Russian patients with stable coronary heart disease

Abstract

Aim. To identify the factors determining homocysteine (HMC) levels in Russian patients with stable coronary heart disease (CHD). Material and methods. The study included 506 patients (388 men; mean age 59,4±12,2 years) with stable CHD. Classical risk factors (RFs) of cardiovascular disease (CVD), renal function (creatinine clearance by Cockroft-Gault formula), and atherosclerotic pathology of other localizations were assessed. The levels of plasma HMC, folate, and cobalamin were measured. Genetic analysis was performed using the real-time polymerase chain reaction method. Results. In 432 patients (85,4 %), hyperhomocysteinemia was diagnosed. The mean HMC level was 14,3±4,6 mkmol/l. According to multifactor analysis results, HMC level was independently associated with folate level (beta coefficient -3,86, p<0,0001), cobalamin level (beta -5,73, p<0,0001), and MTRR 66AA genotype (beta 10,71, p<0,0005). In addition, HMC concentration was linked to the following combinations: MTRR 66G allele + folate level (beta 1,12, p<0,0001), MTRR 66AA allele + cobalamin level (beta 0,012, p<0,0001), TCN 776G allele + cobalamin level (beta -0,03, p<0,0001), TCN 776G allele + folate level (beta 0,58, p<0,0009), MTR 2756G allele + cobalamin level (beta 0,004, p<0,002), MTRR 66G allele + creatinine clearance <90 ml/min (beta 0,08, p<0,001), and TCN 776G allele + creatinine clearance <90 ml/min (beta 0,07, p<0,0007). Conclusion. In Russian patients with stable CHD, HMC level was associated with folate and cobalamin concentrations and MTRR 66AA genotype, as well as with MTR 2756G, MTRR 66G, and TCN 776G alleles combined with vitamin concentrations and renal function.

About the Authors

O. O. Shakhmatova
Russian Cardiology Scientific and Clinical Complex
Russian Federation


A. L. Komarov
Russian Cardiology Scientific and Clinical Complex
Russian Federation


D. V. Rebrikov
DNA-Technology Company; N.I. Vavilov Institute of General Genetics; Russian Academy of Sciences
Russian Federation


M. A. Turchaninova
DNA-Technology Company
Russian Federation


T. I. Kotkina
Russian Cardiology Scientific and Clinical Complex
Russian Federation


A. V. Bolvacheva
Russian Cardiology Scientific and Clinical Complex
Russian Federation


A. D. Deev
State Research Centre f or Preventive Medicine. Moscow
Russian Federation


A. B. Dobrovolsky
Russian Cardiology Scientific and Clinical Complex
Russian Federation


E. V. Titaeva
Russian Cardiology Scientific and Clinical Complex
Russian Federation


E. A. Panchenko
Russian Cardiology Scientific and Clinical Complex
Russian Federation


References

1. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288(16): 2015-22.

2. Selhub J. Homocysteine metabolism. Ann Rev Nutr 1999; 19: 217-46.

3. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111-28.

4. Stanger O, Herrmann W, Pietrzik K, et al. DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003; 41(11): 1392-403.

5. Kothekar MA. Homocysteine in cardiovascular disease: A culprit or an innocent bystander? Indian J Med Sci 2007; 61: 361-71.

6. Fácila L, Nuñez JE, Sanchis J, et al. Early determination of homocysteine levels in acute coronary syndromes, is it an independent prognostic factor? Int J Cardiol 2005; 100(2): 275-9.

7. Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocysteinemia in patients with chronic renal failure. Kidney Int 1997; 52: 495-502.

8. Bostom A, Brosnan JT, Hall B, et al. Net uptake of plasma homocysteine by the rat kidney in vivo. Atherosclerosis 1995; 116: 59-62.

9. В. Б. Спиричев Теоретические и практические аспекты современной витаминологии. Вопр питания 2005; 74: 32-40.

10. Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 34: 1449-54.

11. Rader JI. Folic acid fortification, folate status and plasma homocysteine. J Nutr 2002; 132: 2466-70.

12. Allen LH. The most common explanations for poor vitamin B12 status are low dietary intake of animal-source foods, alcohol consumption, stomach ulcers (helicobacter pylori infection), lactation and poor gut absorption. Causes of vitamin B12 and folate deficiency. Food Nutr Bull 2008; 29(2 Suppl): S20—34; discussion S35-7.

13. Homocysteine, folic acid and B vitamins as secondary prophylaxis. A commentary on current therapy trials by Olaf Stanger. (German, Austrian, and Swiss Homocysteine Society; www. dach-liga-homocystein.org).

14. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10: 111-3.

15. Laraqui A, Allami A, Carrié A, et al. Influence of methionine synthase (A2756G) and methionine synthase reductase (A66G) polymorphisms on plasma homocysteine levels and relation to risk of coronary artery disease. Acta Cardiol 2006; 61(1): 51-61.

16. Kerkeni M, Addad F, Chauffert M, et al. Hyperhomocysteinaemia, methylenetetrahydrofolate reductase polymorphism and risk of coronary artery disease. Ann Clin Biochem 2006; 43(Pt 3): 200-6.

17. Huh HJ, Chi HS, Shim EH, et al. Gene-nutrition interactions in coronary artery disease: correlation between the MTHFR C677T polymorphism and folate and homocysteine status in a Korean population. Thromb Res. 2006; 117(5): 501-6.

18. Guéant-Rodriguez RM, Juilliére Y, Candito M et al. Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. Thromb Haemost 2005; 94(3): 510-5.

19. Brandalize APC, Bandinelli E, Borba JB, et al. Polymorphisms in genes MTHFR, MTR and MTRR are not risk factors for cleft lip/palate in South Brazil. Braz J Med Biol Res 2007; 40: 787-91.

20. Doolin MT, Bardaux S, McDonneli M, et al. Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet 2002; 71: 1222-6.

21. Hubner RA, Muir KR, Liu JF, et al. Folate Metabolism Polymorphisms influence risk of colorectal adenoma reccurence. Cancer Epidemiol Biomarkers Prev 2006; 15(9): 1607-12.

22. Kölling K, Ndrepepa G, Koch W, et al. Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease. Am J Cardiol 2004; 93: 1201-6.

23. Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C-T Polymorphism and risk of coronary heart disease. JAMA 2002; 288: 2023-31.

24. Guéant-Rodriguez RM, Juilliére Y, Candito M, et al. Association of MTRRA66G polymorphism (but not of MTHFR C677T and A1298C, MTRA2756G, TCN C776G) with homocysteine and coronary artery disease in the French population. Thromb Haemost 2005; 94: 510-15.

25. Olteanu H, Munson T, Banerjee R. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochem 2002; 41: 13378-85.

26. Koutmos M, Dattaa S, Pattridgea KF, et al. Insights into the reactivation of cobalamin-dependent methionine synthase. Proc Natl Acad Sci USA 2009; 106(44): 18527-32.


Review

For citations:


Shakhmatova O.O., Komarov A.L., Rebrikov D.V., Turchaninova M.A., Kotkina T.I., Bolvacheva A.V., Deev A.D., Dobrovolsky A.B., Titaeva E.V., Panchenko E.A. Factors determining homocysteine levels in Russian patients with stable coronary heart disease. Cardiovascular Therapy and Prevention. 2010;9(4):49-58. (In Russ.)

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ISSN 2619-0125 (Online)