DOI: https://doi.org/10.22263/2312-4156.2016.5.27
Pavlyushchik O.O.*, Afonin V.Y.*, Chak T.A.*, Sorokina V.N.**, Khapalyuk A.V.**
The association of superoxide dismutase SOD2 gene polymorphism T1183C with metabolic syndrome
*Institute of Bioorganic Chemistry of the Belarusian National Academy of Sciences, Minsk, Republic of Belarus
**Belarusian State Medical University, Minsk, Republic of Belarus
Vestnik VGMU. 2016;15(5):27-35.
Abstract.
Objectives. To evaluate the association between the development of metabolic syndrome and polymorphisms of oxidation-reduction system genes: markers C1167T of catalase gene CAT (rs769217), T1183C of superoxide dismutase gene SOD2 (rs4880), G172A of superoxide dismutase gene SOD3 (rs2536512).
Material and methods. Genotypes were determined with polymerase chain reaction-restriction fragment length polymorphism method in 81 male patients with diagnosed essential hypertension, type 2 diabetes mellitus and with waist circumference ≥ 94 cm. The control group consisted of 64 male donors without any cardiovascular or metabolic disorders. Biometric and biochemical data were obtained.
Results. We found that the allele C of the SOD2 gene is associated with an increased risk of metabolic syndrome development (OR 2,09, 95% CI 1,25 – 3,47, p<0,05). The distribution of SOD2 genotypes made up TT – 17,3%, TC – 55,6%, CC – 27,2 % and TT – 37,5 %, TC – 48,4%, CC – 14,1% in the group of patients with metabolic syndrome and the control group, respectively (t2=8,79, p<0,05). Patients with the TT genotype had lower levels of red blood cells (p<0,05) and hemoglobin (p>0,05) in comparison with the C allele carriers, which may indicate the lack of oxygen in tissues and response stimulation of erythropoietin release in C allele patients. There was no association of SOD3 and CAT gene alleles with metabolic syndrome.
Conclusions. The obtained results suggest that the SOD2 gene polymorphism T1183C is an important determining factor in the risk of metabolic syndrome development and erythrocytes level in male population of Belarus. On further investigation the polymorphism may be used for the elaboration and early application of preventive strategies and the formation of groups of patients with a higher risk of complications development.
Key words: metabolic syndrome, red blood cells, hemoglobin, polymorphism Val16Ala, superoxide dismutase, catalase.
References
1. Stančáková A, Laakso M. Genetics of metabolic syndrome. Rev Endocr Metab Disord. 2014 Dec;15(4):243-52. doi: http://dx.doi.org/10.1007/s11154-014-9293-9
2. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct;120(16):1640-5. doi: http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644
3. Rotar' OP, Libis RA, Isaeva EN, Erina AM, Shavshin DA, Moguchaya EV, i dr. Prevalence of a metabolic syndrome in the different cities of the Russian Federation. Ros Kardiol Zhurn. 2012;(2):55-62. (In Russ.)
4. Bellia A, Giardina E, Lauro D, Tesauro M, Di Fede G, Cusumano G, et al. “The Linosa Study”: epidemiological and heritability data of the metabolic syndrome in a Caucasian genetic isolate. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):455-61. doi: http://dx.doi.org/10.1016/j.numecd.2008.11.002
5. Sá da Fonseca LJ, Nunes-Souza V, Guedes GS, Schettino-Silva G, Mota-Gomes MA, Antas Rabelo L. Oxidative status imbalance in patients with metabolic syndrome: role of the myeloperoxidase/hydrogen peroxide axis. Oxid Med Cell Longev. 2014. doi: http://dx.doi.org/10.1155/2014/898501
6. Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life Sci. 2009 May;84(21-22):705-12. doi: http://dx.doi.org/10.1016/j.lfs.2009.02.026
7. Biino G, Parati G, Concas MP, Adamo M, Angius A, Vaccargiu S, et al. Environmental and genetic contribution to hypertension prevalence: data from an epidemiological survey on Sardinian genetic isolates. PLoS One. 2013;8(3):e59612. doi: http://dx.doi.org/10.1371/journal.pone.0059612
8. Tamai M, Furuta H, Kawashima H, Doi A, Hamanishi T, Shimomura H, et al. Extracellular superoxide dismutase gene polymorphism is associated with insulin resistance and the susceptibility to type 2 diabetes. Diabetes Res Clin Pract. 2006 Feb;71(2):140-5. doi: http://dx.doi.org/10.1016/j.diabres.2005.05.006
9. Mansego ML, De Marco G, Ivorra C, Lopez-Izquierdo R, Morcillo S, Rojo-Martínez G, et al. The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study. J Transl Med. 2015 Sep;13:286. doi: http://dx.doi.org/10.1186/s12967-015-0652-4
10. Hurs LD. Molecular genetics: The sound of silence. Nature. 2011 Mar;471(7340):582-3. doi: http://dx.doi.org/10.1038/471582a
11. Góth L, Nagy T, Paragh G, Káplár M. Blood catalase activities, catalase gene polymorphisms and acatalasemia mutations in Hungarian patients with diabetes mellitus. Glob J Obes Diabetes Metab Syndr. 2016;3(1):001-5. doi: http://dx.doi.org/10.17352/2455-8583.000011
12. Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D, Degoul F. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics. 2003 Mar;13(3):145-57.
13. Bastaki M, Huen K, Manzanillo P, Chande N, Chen C, Balmes JR, et al. Genotype-activity relationship for Mn-superoxide dismutase, glutathione peroxidase 1 and catalase in humans. Pharmacogenet Genomics. 2006 Apr;16(4):279-86. doi: http://dx.doi.org/10.1097/01.fpc.0000199498.08725.9c
14. Hsueh YM, Lin P, Chen HW, Shiue HS, Chung CJ, Tsai CT, et al. Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension. J Toxicol Environ Health A. 2005 Sep;68(17-18):1471-84. doi: http://dx.doi.org/10.1080/15287390590967414
15. Chistyakov DA, Savost'anov KV, Zotova EV, Nosikov VV. Polymorphisms in the Mn-SOD and EC-SOD genes and their relationship to diabetic neuropathy in type 1 diabetes mellitus. BMC Med Genet. 2001;2:4.
16. Jelkmann W. Regulation of erythropoietin production. J Physiol. 2011 Mar;589(Pt 6):1251-8. doi: http://dx.doi.org/10.1113/jphysiol.2010.195057
17. Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005 Mar;115(3):500-8.
Information about authors:
Pavlyushchik O.O. – associate research officer of Pharmacogenetics Laboratory, postgraduate, Institute of Bioorganic Chemistry of the Belarusian National Academy of Sciences;
Afonin V.Y. – Candidate of Biological Sciences, head of Pharmacogenetics Laboratory, Institute of Bioorganic Chemistry of the Belarusian National Academy of Sciences;
Chak T.A. – postgraduate of the Chair of Clinical Pharmacology, Belarusian State Medical University;
Sorokina V.N. – postgraduate of the Chair of Clinical Pharmacology, Belarusian State Medical University;
Khapalyuk A.V. – Doctor of Medical Sciences, professor, head of the Chair of Clinical Pharmacology, Belarusian State Medical University.
Correspondence address: Republic of Belarus, 220141, Minsk, 5/2 academician V.F. Kuprevich str., Pharmacogenetics Laboratory, Institute of Bioorganic Chemistry of the Belarusian National Academy of Sciences. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Pavlyushchik Olena O.
