Pathogenesis of atherosclerosis of arteries of the lower extremities: candidate genes and their polymorphism

Abstract

Personalized medicine involves the use of genetic methods by physicians for early diagnosis, prediction of the nature of the disease course and the choice of medicines and their doses based on personalized characteristics of the individual patient. Advances in the study of the human genome make it possible to reveal the interrelation between different varieties of alleles of human genes (polymorphism) and predisposition to certain diseases. Currently there are more than 10 million single-nucleotide polymorphisms in the human genome, but their biological role remains poorly understood. On the basis of a literature search of electronic full-text and abstract-only versions of articles’, which was conducted in the PUBMED, OMIM and GENE databases, collected was the information on genetic predisposition to systemic atherosclerosis. The review is dedicated to polymorphisms of the major genes that play a role in the pathophysiology of atherosclerosis of the lower extremities.

Keywords

gene polymorphism / pathophysiology of systemic atherosclerosis / ischemic heart disease

References

[1] Кленкова Н.А., Салтыкова Н.Б., Шмелёва В.М., Блинов М.Н. Особенности аллельного полиморфизма генов метаболизма гомоцистеина и фолатов у больных с атеросклерозом аретрий нижних конечностей // Вестн. хир. им. И.И. Грекова. - 2009. - Т. 168, №6. - С. 41-44.

[2] Лилли Л. Патофизиология заболеваний сердечно-сосудистой системы / Пер. с англ. под ред. Д.М. Аронова. - Москва: БИНОМ, 2003. - 598 с.

[3] Торшин И.Ю., Громова О.А. Сосудистые заболевания сердца, мозга и молекулярные гены. Часть 1. Ассоциативные исследования и патофизиология сосудистых заболеваний // Трудный пациент. - 2008. - №2. - С. 15-18.

[4] Catalano M., Cortelazzo A., Yilmaz Y. et al. The LPA gene C93T polymorphism influences plasma lipoprotein(a) levels and is independently associated with susceptibility to peripheral arterial disease // Clin. Chim. Acta. - 2008. - Vol. 387. - P. 109-112.

[5] Criqui M.H., Langer R.D., Fronek A. et al. Mortality over a period of 10 years in patients with peripheral arterial disease // N. Engl. J. Med. - 1992. - Vol. 326. - P. 381-386.

[6] Eller P., Schgoer W., Mueller T. et al. The K121Q polymorphism of ENPP1 and peripheral arterial disease // Heart Vess. - 2008. - Vol. 23. - P. 104-107.

[7] Eller P., Schgoer W., Mueller T. et al. Hepatic lipase polymorphism and increased risk of peripheral arterial disease // J. Intern. Med. - 2005. - Vol. 258. - P. 344-348.

[8] Flex A., Gaetani E., Angelini F. et al. Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia // J. Intern. Med. - 2007. - Vol. 262. - P. 124-130.

[9] Folsom A.R., Peacock J.M., Boerwinkle E. Variation in PCSK9, low LDL cholesterol, and risk of peripheral arterial disease // Atherosclerosis. - 2009. - Vol. 202. - P. 211-215.

[10] Gudmundsson G., Matthiasson S.E., Arason H. et al. Localization of a gene for peripheral arterial occlusive disease to chromosome 1p31 // Am. J. Hum. Genet. - 2002. - Vol. 70. - P. 586-592.

[11] Khandanpour N., Willis G., Meyer F.J. et al. Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis // J. Vasc. Surg. - 2009. - Vol. 49. - P. 711-718.

[12] Kim R.J., Becker R.C. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: a meta-analysis of published studies // Am. Heart J. - 2003. - Vol. 146. - P. 948-957.

[13] Kullo I.J., Greene M.T., Boerwinkle E. et al. Association of polymorphisms in NOS3 with the ankle-brachial index in hypertensive adults // Atherosclerosis. - 2008. - Vol. 196. - P. 905-912.

[14] Ledmyr H., McMahon A.D., Ehrenborg E. et al. The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease // Circulation. - 2004. - Vol. 109. - P. 2279-2284.

[15] Monsalve M.V., Young R., Jobsis J. et al. DNA polymorphisms of the gene for apolipoprotein B in patients with peripheral arterial disease // Atherosclerosis. - 1988. - Vol. 70. - P. 123-129.

[16] Ritsch A., Sonderegger G., Sandhofer A. et al. Scavenger receptor class B type I polymorphisms and peripheral arterial disease // Metabolism. - 2007. - Vol. 56. - P. 1135-1141.

[17] Rossi E., Biasucci L.M., Citterio F. et al. Risk of myocardial infarction and angina in patients with severe peripheral vascular disease: predictive role of C-reactive protein // Circulation. - 2002. - Vol. 105. - P. 800-803.

[18] Sabino A., Fernandes A.P., Lima L.M. et al. Polymorphism in the methylenetetrahydrofolate reductase (C677T) gene and homocysteine levels: a comparison in Brazilian patients with coronary arterial disease, ischemic stroke and peripheral arterial obstructive disease // J. Thromb. Thrombolysis. - 2009. - Vol. 27. - P. 82-87.

[19] Schgoer W., Eller P., Mueller T. et al. The MTP-493TT genotype is associated with peripheral arterial disease: results from the Linz Peripheral Arterial Disease (LIPAD) Study // Clin. Biochem. - 2008. - Vol. 41. - P. 712-716.

[20] Shammas N.W., Dippel E.J. Evidence-based management of peripheral vascular disease // Curr. Atheroscler. Rep. - 2005. - Vol. 7. - P. 358-363.

[21] Sofi F., Lari B., Rogolino A. et al. Thrombophilic risk factors for symptomatic peripheral arterial disease // J. Vasc. Surg. - 2005. - Vol. 41. - P. 255-260.

[22] Sticchi E., Sofi F., Romagnuolo I. et al. eNOS and ACE genes influence peripheral arterial disease predisposition in smokers // J. Vasc. Surg. - 2010. - Vol. 52. - P. 97-102.

[23] Tseng C.H. Lipoprotein(a) is an independent risk factor for peripheral arterial disease in Chinese type 2 diabetic patients in Taiwan // Diabetes Care. - 2004. - Vol. 27. - P. 517-521.

[24] Valdivielso P., Ariza M.J., de la Vega-Roman C. et al. Association of the -250G/A promoter polymorphism of the hepatic lipase gene with the risk of peripheral arterial disease in type 2 diabetic patients // J. Diabet. Complic. - 2008. - Vol. 22. - P. 273-277.

[25] Weitz J.I., Byrne J., Clagett G.P. et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review // Circulation. - 1996. - Vol. 94. - P. 3026-3049.

RIGHTS & PERMISSIONS

Katina M.N., Gayfullina R.F., Valiullin V.V., Rizvanov A.A.