REMODELING OF CARDIOVASCULAR SYSTEM AND DEVELOPMENT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH METABOLIC SYNDROME AND OBESITY: ROLE OF GENES ENOS, SUBUNIT P22-PHOX OF NADPH-OXIDASE AND MTHFR


Cite item

Full Text

Abstract

Aim. To examine contribution of polymorphisms of genes of endothelial NO-synthase (eNOS), NADPH-oxidase and methylenetetrahydrofolate reductase (mTHFR) to development of remodeling of cardiovascular system and chronic disease of the kidneys (CDK) in patients with metabolic syndrome (mS) and obesity. Material and methods. Standard clinical and device examinations were made and polymorphisms C242T of gene of subunit p22-phox of NADPH-oxidase, G894T of gene of eNOS and C677T of gene of MTHFR were studied in 66 MS patients (49 males and 17 females, age 19-62 years. Results. The presence of even one prognostically poor allele variants of the genes studied was registered in 83 examinees. The genotype 242TT p22-phox of NADPH-oxidase subunit was associated with the highest insulin resistance, allele 894T of gene eNOS - with reduced glomerular filtration rate and progression of left ventricular hypertrophy. Conclusion. Polymorphism of the genes the products of which modulate endothelial function can be considered as potential predictors of severity of MS target organs impairment.

About the authors

E A Saginova

I.M. Sechenov First Moscow State Medical University

Email: med02@yandex.ru
Chair of Therapy and Occupational Diseases of Medicoprophylactic Department

M G Gallyamov

M.V. Lomonosov Moscow State University

Chair of Internal Medicine of Fundamental Medicine Department

A V Balatsky

M.V. Lomonosov Moscow State University

Chair of Biochemistry and Molecular Medicine of Fundamental Medicine Department

A V Kolotvin

M.V. Lomonosov Moscow State University

Chair of Biochemistry and Molecular Medicine of Fundamental Medicine Department

M V Severova

I.M. Sechenov First Moscow State Medical University

Chair of Therapy and Occupational Diseases of Medicoprophylactic Department

L M Samokhodskaya

M.V. Lomonosov Moscow State University

Laboratory of Gene and Cell Technology of Fundamental Medicine Department

V V Fomin

I.M. Sechenov First Moscow State Medical University

Chair of Therapy and Occupational Diseases of Medicoprophylactic Department

T N Krasnova

M.V. Lomonosov Moscow State University

Chair of Internal Medicine of Fundamental Medicine Department

N A Mukhin

I.M. Sechenov First Moscow State Medical University

Chair of Therapy and Occupational Diseases of Medicoprophylactic Department

References

  1. Чазова И. Е., Мычка В. Б. Метаболический синдром. М.: Медиа Медика; 2004.
  2. Kerr S.M., Livingstone M.B., McCrorie T.A., Wallace J.M. Endothelial dysfunction associated with the obesity and the effect of weight loss interventions. Proc.Nutr. Soc. 2011; 70 (4): 418—425.
  3. Blanquicett C., Graves A., Kleinhenz D. J., Hart C. M. Attenuation of signaling and nitric oxid production following prolonged leptin exposure in human aortic endothelial cells. J. Invest. Med. 2007; 55 (7): 368—377.
  4. Fortuflo А., Jose G. S., Moreno M. U. et al. Phagocytic NADPH oxidase overactivity underlies oxidative stress in metabolic syndrome. Diabetes 2006; 55: 209—215.
  5. Комитет экспертов РМОАГ/ВНОК. Диагностика и лечение артериальной гипертензии (Рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов). Систем. гипертензии 2010; 3: 5—26.
  6. Foppa M., Duncan B. B., Rohde L. E. Echocardiography-based left ventricular mass estimation. How should we define hypertrophy? Cardiovasc Ultrasound 2005; 3: 17.
  7. Kidney Disease Outcome Quality Initiative. Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am. J. Kidney Dis. 2002; 39 (Suppl. 2): S1—S246.
  8. Самоходская Л. М., Балацкий А. В., Садекова О. Н., Таратина О.В. Значение генетических и средовых факторов в развитии мультифакториальных заболеваний. М.; 2011. 258—263.
  9. Сhen J., Muntner P., Hamm L. et al. The metabolic syndrome and chronic kidney disease in U. S. adults. Ann. Intern. Med. 2004; 140: 167—174.
  10. Wolf G., Hamann A., Han D. C. et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis. Kidney Int. 1999; 6 (3): 860—872.
  11. Bruce K.D., Byrne C.D. The metabolic syndrome: common origins of a multifactorial disorder. Postgrad. Med. J. 2009; 85 (1009): 614—621.
  12. He M. A., Cheng L. X., Jiang C. Z. Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China. Am. Heart J. 2007; 153 (4): 640e1—640e6.
  13. Ueno T., Watanabe H., Fukuda N. et al. Influence of genetic polymorphisms in oxidative stress related genes and smoking on plasma MDA-LDL, soluble CD40 ligand, E-selectin and soluble ICAM1 levels in patients with coronary artery disease. Med. Sci. Monit. 2009; 15 (7): CR341—CR348.
  14. Ji L., Fu F., Zhang L. et al. Insulin attenuates myocardial ischemia/ reperfusion injury via reducing oxidative/nitrative stress. Am. J. Physiol. Endocrinol. Metab. 2010; 298 (4): 2416—2423.
  15. Dandona P., Ghanim H., Bandyopadhyay H. et al. Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans. Diabetes Care 2010; 33 (11): 2416—2423.
  16. Zintzaras E., Papathanasiou A.A., Stefanidis I. Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: a HuGE review and meta-analysis. Genet. Med. 2009; 11 (10): 695—706.
  17. Ezzidi I., Mtiraoui N., Mohamed M. B. et al. Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and -786T>C gene variants with diabetic nephropathy. J. Diabet. Complicat. 2008; 22 (5): 331—338.
  18. Ahluwalia T. S., Ahuja M., Rai T. S. et al. Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. Mol. Cell. Biochem. 2008; 314 (1—2): 9—17.
  19. Zhu H., Wang X., Dong Y. et al. Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth. Pharmacogenet. Genom. 2005; 15 (9): 669—675.
  20. Lapu-Bura R. Quarshie A., Lyn D. et al. The 894T allele of endothelial nitric oxide synthase gene is related to left ventricular mass in African Americans with high-normal blood pressure. J. Natl. Med. Assoc. 2005; 97 (2): 197—205.
  21. Kazakov A., Müller P., Jagoda P. et al. Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis. Cardiovasc. Res. 2011; Dec. 11. [Epub ahead of print]
  22. van Guldener C., Robinson K. Homocysteine and renal disease. Semin. Thromb. Hemost. 2000; 26 (3): 313—324.

Copyright (c) 2012 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies