Ecological geneticsEcological geneticsЭкологическая генетика1811-09322411-9202Eco-Vector7030310.17816/ecogen70303Human ecological geneticsЭкологическая генетика человекаResearch ArticleAssociation of VEGF +405 C > G (rs2010963) polymorphism with susceptibility of metabolic syndrome: Cardio-metabolic risk factors and serum Matrix Metaloproteinase-3 concentrationsАссоциация полиморфизма +405C > G (rs2010963) с подверженностью к метаболическому синдрому: кардио-метаболические факторы риска и концентрация матриксной металлопротеиназы-325031589500NikniazLeilaНикниазЛейла
Iran, Islamic Republic of
nikniaz@yahoo.comAbbasalizad-FarhangiMahdiehАббасализад-ФархангиМахди
Iran, Islamic Republic of
abbasalizad_m@yahoo.comTabriz Health Services Management Research CenterИсследовательский центр Управления Медицинскими услугамиTabriz University of Medical SciencesТебризский университет медицинских наук25082021101020211932632710705202125082021Copyright ©; 2021,Copyright ©; 2021, ООО "Эко-Вектор"2021ООО "Эко-Вектор"https://journals.eco-vector.com/ecolgenet/article/view/70303

BACKGROUND: In the present study we investigated the role of +405 VEGF gene polymorphism in the pathogenesis of metabolic syndrome and to explore its association with several biochemical risk factors.

MATERIALS AND METHODS: VEGF +405 single nucleotide polymorphism were genotyped in 150 patients with metabolic syndrome and 50 healthy individuals using the PCR-RFLP method. Serum levels of biochemical variables were assessed by commercial ELISA technique.

RESULTS: GC genotype was more prevalent among patients with metabolic syndrome. In GC genotype, patients with metabolic syndrome had higher waist to hip ratio, WHR, triglyceride, and lower high density lipoprotein and alanine aminotransferase concentrations compared with the control group.

CONCLUSIONS: The current study demonstrated that +405 VEGF gene polymorphism was a potent predictor of metabolic abnormalities in patients with metabolic syndrome. Further studies with larger sample size are needed to clarify these associations properly.

В настоящем исследовании мы изучали роль нуклеотидной замены +405 в гене VEGF в патогенезе метаболического синдрома и анализировали ее связь с несколькими биохимичесимим факторами риска. Было генотипировано 150 пациентов с метаболическим синдромом и 50 здоровых людей с помощью PCR-RFLP. Биохимические показатели в сыворотке оценивали с помощью ELISA. Среди пациентов с метаболическим синдромом преобладал генотип CG. У них же было повышено содержание триглицеридов, снижено содержание липопротеинов высокой плотности и аланинаминотрансферазы. Показано, что изучаемая замена может быть предиктором метаболических нарушений при метаболическом синдроме. Подтверждение этого вывода требует увеличения выборки.

genetic variantsmetabolic syndromevascular endothelial growth factorгенетические вариантыметаболический синдромсосудистый эндотелиальный фактор ростаReaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–1607. DOI: 10.2337/diab.37.12.1595Heshmat R, Hemati Z, Qorbani M, et al. Metabolic syndrome and associated factors in Iranian children and adolescents: the CASPIAN-V study. J Cardiovasc Thorac Res. 2018;10(4):214–220. DOI: 10.15171/jcvtr.2018.37Zhang X, Lerman LO. The metabolic syndrome and chronic kidney disease. Transl Res. 2017;183:14–25. DOI: 10.1016/j.trsl.2016.12.004Kim D, Touros A, Kim WR. Nonalcoholic fatty liver disease and metabolic syndrome. Clinics in liver disease. 2018;22(1):133–140. DOI: 10.1016/j.cld.2017.08.010Ghanei Gheshlagh R, Parizad N, Sayehmiri K. The relationship between depression and metabolic syndrome: systematic review and meta-analysis study. Iran Red Crescent Med J. 2016;18: e26523-e. DOI: 10.5812/ircmj.26523Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk: A systematic review and meta-analysis. J Am Coll Cardiol. 2010;56(14):1113–1132. DOI: 10.1016/j.jacc.2010.05.034Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356–359. DOI: 10.1001/jama.287.3.356Zabetian A, Hadaegh F, Azizi F. Prevalence of metabolic syndrome in Iranian adult population, concordance between the IDF with the ATP III and the WHO definitions. Diabetes Res Clin Pract. 2007;77(2) 251–257. DOI: 10.1016/j.diabres.2006.12.001Miyazawa-Hoshimoto S, Takahashi K, Bujo H, et al. Elevated serum vascular endothelial growth factor is associated with visceral fat accumulation in human obese subjects. Diabetologia. 2003;46:1483–1488. DOI: 10.1007/s00125-003-1221-6Watson CJ, Webb NJ, Bottomley MJ, Brenchley PE. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000;12(8):1232–1235. DOI: 10.1006/cyto.2000.0692Kim YR, Hohong S. Association between the polymorphisms of the vascular endothelial growth factor gene and metabolic syndrome. Biomed Rep. 2015;3(3):319–326. DOI: 10.3892/br.2015.423Moradzadegan A, Vaisi-Raygani A, Nikzamir A, Rahimi Z. Angiotensin converting enzyme insertion/deletion (I/D)(rs4646994) and Vegf polymorphism (+405G/C; rs2010963) in type II diabetic patients: Association with the risk of coronary artery disease. J Renin Angiotensin Aldosterone Syst. 2015;16:672–680. DOI: 10.1177/1470320313497819Ray D, Mishra M, Ralph S, et al. Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Diabetes. 2004;53(3):861–864. DOI: 10.2337/diabetes.53.3.861Zafar MI, Mills K, Ye X, et al. Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components: a systematic review and meta-analysis. Diabetology & metabolic syndrome. 2018;10:62–72. DOI: 10.1186/s13098-018-0363-0Siervo M, Ruggiero D, Sorice R, et al. Body mass index is directly associated with biomarkers of angiogenesis and inflammation in children and adolescents. Nutrition. 2012;28(3):262–266. DOI: 10.1016/j.nut.2011.06.007Kimura K, Hashiguchi T, Deguchi T, et al. Serum VEGF – as a prognostic factor of atherosclerosis. Atherosclerosis. 2007;194(1):182–188. DOI: 10.1016/j.atherosclerosis.2006.07.025Szaflik JP, Wysocki T, Kowalski M, et al. An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246:39–43. DOI: 10.1007/s00417-007-0674-6Petrovič D, Verhovec R, Petrovič MG, et al. Association of vascular endothelial growth factor gene polymorphism with myocardial infarction in patients with type 2 diabetes. Cardiology. 2007;107(4):291–295. DOI: 10.1159/000099064Hagberg CE, Mehlem A, Falkevall A, et al. Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes. Nature. 2012;490:426–430. DOI: 10.1038/nature11464Kanaki T, Bujo H, Mori S, et al. Functional analysis of aortic endothelial cells expressing mutant PDGF receptors with respect to expression of matrix metalloproteinase-3. Biochem Biophys Res Commun. 2002;294(2):231–237. DOI: 10.1016/S0006-291X(02)00468-0Silvestre JS, Mallat Z, Tamarat R, et al. Regulation of matrix metalloproteinase activity in ischemic tissue by interleukin-10: role in ischemia-induced angiogenesis. Circ Res. 2001;89(3):259–264. DOI: 10.1161/hh1501.094269Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 2001;11(1): S37–S43. DOI: 10.1016/S0962-8924(01)82222-4Murphy G, Nagase H. Localizing matrix metalloproteinase activities in the pericellular environment. FEBS J. 2011;278(1):2–15. DOI: 10.1111/j.1742-4658.2010.07918.xThorp E. Contrasting inflammation resolution during atherosclerosis and post myocardial infarction at the level of monocyte/macrophage phagocytic clearance. Front Immunol. 2012;3:39–49. DOI: 10.3389/fimmu.2012.00039Lijnen HR, Maquoi E, Demeulemeester D, et al. Modulation of fibrinolytic and gelatinolytic activity during adipose tissue development in a mouse model of nutritionally induced obesity. Thromb Haemost. 2002;88(2):345–353. DOI: 10.1055/s-0037-1613208Gummesson A, Hägg D, Olson FJ, et al. Adipose tissue is not an important source for matrix metalloproteinase-9 in the circulation. Scand J Clin Lab Invest. 2009;69:636–642. DOI: 10.3109/00365510902912747Miksztowicz V, Muzzio ML, Royer M, et al. Increased plasma activity of metalloproteinase 2 in women with metabolic syndrome. Metabolism. 2008;57(11):1493–1496. DOI: 10.1016/j.metabol.2008.06.001Cicero AFG, Derosa G, Manca M, et al. Vascular remodeling and prothrombotic markers in subjects affected by familial combined hyperlipidemia and/or metabolic syndrome in primary prevention for cardiovascular disease. Endothelium. 2007;14(4–5):193–198. DOI: 10.1080/10623320701606731Barylski M, Kowalczyk E, Banach M, et al. Plasma total antioxidant activity in comparison with plasma NO and VEGF levels in patients with metabolic syndrome. Angiology. 2009;60(1): 87–92. DOI: 10.1177/0003319708327165Farzi A, Hagh MF. Association between Vascular Endothelial Growth Factor (VEGF) +405 C/G polymorphism and hypertension in North West of Iran. Int Res J App Bas Sci. 2014;8:122–125.Buraczynska M, Ksiazek P, Baranowicz-Gaszczyk I, Jozwiak L. Association of the VEGF gene polymorphism with diabetic retinopathy in type 2 diabetes patients. Nephrol Dial Transplant. 2007;22(3):827–832. DOI: 10.1093/ndt/gfl641Jahangiry L, Shojaeizadeh D, Najafi M, et al. ‘Red Ruby’: an interactive web-based intervention for lifestyle modification on metabolic syndrome: a study protocol for a randomized controlled trial. BMC Public Health. 2014;14:748–754. DOI: 10.1186/1471-2458-14-748Jahangiry L, Shojaeizadeh D, Najafi M, et al. ‘Red Ruby’: an interactive web-based intervention for lifestyle modification on metabolic syndrome: a study protocol for a randomized controlled trial. BMC public health. 2014;14(1):748. DOI: 10.1186/1471-2458-14-748Farhangi MA, Jahangiry L, Mirinazhad MM, et al. A web-based interactive lifestyle modification program improves lipid profile and serum adiponectin concentrations in patients with metabolic syndrome: the “Red Ruby” study. Int J Diab Dev C. 2015;37:21–30. DOI: 10.1007/s13410-015-0395-zMirinazhad MM, Farhangi MA, Jahangiri L, Yaghoubi A. Serum adiponectin concentrations in relation to lipid proffle, anthropometric variables and insulin resistance in patients with metabolic syndrome. Malay J Nutr. 2014;20:283–289.Douvaras P, Antonatos DG, Kekou K, et al. Association of VEGF gene polymorphisms with the development of heart failure in patients after myocardial infarction. Cardiology. 2009;114(1):11–18. DOI: 10.1159/000210189Miller SA, Dykes DD, Polesky HFRN. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215–1219. DOI: 10.1093/nar/16.3.1215Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002;51(5):1635–1639. DOI: 10.2337/diabetes.51.5.1635Kowalski J, Sliwczyńska-Rodziewicz D, Kowalczyk E, et al. Plasma nitric oxide and vascular endothelial growth factor levels in patients with metabolic syndrome and co-existing vascular complications. Pol Merkur Lekarski. 2011;30:249–252.Altinkaya SO, Ugur M, Ceylaner G, et al. Vascular endothelial growth factor +405 C/G polymorphism is highly associated with an increased risk of endometriosis in Turkish women. Arch Gynecol Obstet. 2011;283:267–272. DOI: 10.1007/s00404-009-1344-1Kim OkJ, Hong SH, Oh SH, et al. Association between VEGF polymorphisms and homocysteine levels in patients with ischemic stroke and silent brain infarction. Stroke. 2011;42(9):2393–2402. DOI: 10.1161/STROKEAHA.110.607739Huez I, Bornes S, Bresson D, et al. New vascular endothelial growth factor isoform generated by internal ribosome entry site-driven CUG translation initiation. Mol Endocrinol. 2001;15(12):2197–2210. DOI: 10.1210/mend.15.12.0738Vander Meer P, de Boer RA, White HL, et al. The VEGF +405 CC promoter polymorphism is associated with an impaired prognosis in patients with chronic heart failure: a MERIT-HF substudy. J Card Fail. 2005;11(4):279–284. DOI: 10.1016/j.cardfail.2004.11.006