ASSOCIATION OF THE VARIANTS OF NUCLEOTIDE SEQUENCE OF THE GENE ADIPOQ WITH PLASMATIC LEVEL OF ADIPONECTIN, THE GRADE OF CORONARY ATHEROSCLEROSIS SEVERITY AND RATE OF CARDIOVASCULAR DISEASES

Aim. The search for genetic markers of ADIPOQ, associated with the level of adiponectin and development of coronary atherosclerosis.

Material and methods. To the study, patients included, who had undergone diagnostic coronary arteriography in 2011-2012 in the NMRCPM with assessment of the severity of coronary atherosclerosis. The level of adiponectin was measured in plasma with the test-system based on the immune enzyme analysis. Genetic variants rs17300539, rs182052 and rs266729 gene ADIPOQ were measured realtime (Applied Biosystems, 7500 Real Time PCR System). Alleles of the studied variants were summarized by a unified score of genetic risk (SGR).

Results. To the study, 447 patients included, of those 319 males (70,7%). Median of age was 61 [55-69] y.o. All patients were selected to 2 groups by SGR (≤2 and >2, respectively). Groups differed by the level of adiponectin 7,64 vs 8,29 mcg/mL (р=0,01), total cholesterol 4,60 vs 5,00 mM/L (p=0,03), cholesterol of low density lipoproteides 2,8 vs 3,09 mM/L (p=0,03), and the rate of unstable angina development 2,15% vs 6,8% (р=0,02) and type 2 diabetes 11,8% vs 21,1% (р=0,01), respectively. There was no difference in the groups by Syntax and Gensini score.

Conclusion. Genetic score based on the three variants of ADIPOQ does determine the plasmatic level of adiponectin and risk of unstable angina and diabetes, but not the grade of coronary atherosclerosis.

1. Kumada M, Kihara K, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003;23:85-9. doi:10.1161/01. ATV.0000048856.22331.50.

2. Hao G, Li W, Guo R, et al. Serum total Adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies. Atherosclerosis. 2013;228:29-35. doi:10.1016/j.atherosclerosis.2013.02.018.

3. Chandran M, Phillips SA, Ciaraldi T, et al. Adiponectin: More than Just Another Fat Cell Hormone. Diabetes Care. 2003 Aug;26(8):2442-50. doi:10.2337/diacare.26.8.2442.

4. Ouchi N, Parker JL, Lugus JJ, et al. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97. doi:10.1038/nri2921.

5. Meshkov AN, Sherbakova NV. Molecular genetic diagnosis of predisposition to the development of coronary heart disease: the current state of the problem. Consilium Medicum. 2016;18(12):22-6. (In Russ.)

6. Meshkov AN, Malyshev PP, Kuharchuk VV. Family hypercholesterolemia in Russia: genetic and phenotypic characteristics. Ther. arch. 2009;81(9):23-8. (In Russ.)

7. Ramya K, Ayyappa KA, Ghosh S, et al. Genetic association of ADIPOQ gene variants with type 2 diabetes, obesity and serum adiponectin levels in south Indian population. Gene. 2013 Dec 15;532(2):253-62. doi:10.1016/j.gene.2013.09.012.

8. Walter K, Min JL, Huang J, et al. The UK10K project identifies rare variants in health and disease. Nature. 2015;526(7571):82-90. doi:10.1038/nature14962.

9. Chepetova TV, Meshkov AN. Hypertriglyceridemia: etiology, pathogenesis, diagnosis. Cardiovascular Therapy and Prevention. 2006;5(5):94-100. (In Russ.)

10. Pei Y, Xu Y, Niu W. Causal relevance of circulating adiponectin with cancer: a meta-analysis implementing Mendelian randomization. Tumor Biol. 2015;36:585-94. doi:10.1007/s13277-014-2654-x.

11. Ghoshal K, Bhattacharyya M. Adiponectin: Probe of the molecular paradigm associating diabetes and obesity. World J Diabetes. 2015 February 15;6(1):151-66. doi:10.4239/wjd.v6.i1.151.

12. Mackevics V, Heid IM, Wagner SA, et al. The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. European Journal of Human Genetics. 2006;14:349-56. doi:10.1038/sj.ejhg.5201552.

13. AlSaleh A, O’Dell SD, Frost GS, et al. Single nucleotide polymorphisms at the ADIPOQ gene locus interact with age and dietary intake of fat to determine serum adiponectin in subjects at risk of the metabolic syndrome. Am J Clin Nutr. 2011;94:262-9. doi:10.3945/ajcn.111.014209.

14. Muiya N, Al-Najai M, Tahir AI, et al. The 3′-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits. BMC Med Genet. 2013;14:127. doi:10.1186/1471-2350-14-127.

15. Mtiraoui N, Ezzidi I, Turki A, et al. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012 Aug;97(2):290-7. doi:10.1016/j.diabres.2012.02.015.

16. Hui S, Ying L, Juan D, et al. Application of Back Propagation Artificial Neural Network on Genetic Variants in Adiponectin ADIPOQ, Peroxisome Proliferator-Activated Receptor-γ, and Retinoid X Receptor-α Genes and Type 2 Diabetes Risk in a Chinese Han Population. Diabetes Technol Ther. 2012 Mar;14(3):293-300. doi:10.1089/dia.2011.0071.

17. Richardson DK, Schneider J, Fourcaudot MJ, et al. Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans. Diabetologia. 2006 Oct;49(10):2317-28. doi:10.1007/s00125-006-0384-3.

18. Gumanova NG, Metelskaya VA, Gavrilova NE, et al. Ratios of leptin to insulin and adiponectin to endothelin are sex-dependently associated with extent of coronary atherosclerosis. Biomarkers. 2017;22(3-4):239-45. doi:10.1080/1354750X.2016.1201539.

19. Gavrilova NE, Metelskaya VA, Ozerova IN, et al. Features of the sub-fraction spectrum of apolipoprotein B-containing lipoproteins in patients with carotid and or coronary atherosclerosis Russ J Cardiol. 2016;21(10):64-70. (In Russ.) . doi:10.15829/1560-4071-2016-10-64-70

20. Diagnostics and therapy of stable angina. Russian guidelines. 2 revision. Cardiovascular therapy and prevention. 2008;7(6), suppl. 4, p. 40. (In Russ.)

21. Rodriguez S, Gaunt TR, Day INM. Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies. Am J Epidemiol. 2009;169(4):50514. doi:10.1093/aje/kwn359