Genetic markers of the metabolic syndrome in the Russian population (based on the ESSE-RF study)

Objective. To assess the relationship of carriers of risk alleles for the rs9939609 polymorphisms of the FTO gene and rs1225537 of the TCF7L2 gene with the metabolic syndrome (MS) component in a national population sample of three regions (Samara, Orenburg, St Petersburg) as part of the ESSE-RF epidemiological study.

Design and methods. The data of 3 regions were analyzed: Samara, Orenburg and St Petersburg. The total number of patients included in the study was 4 793 people, the average age of the examined was 45,6 ± 11,9 years. All participants in the study underwent an assessment of anthropometric parameters (height, weight, waist circumference), blood pressure and heart rate; serum glucose and lipids were measured, genotyping for the determination of single nucleotide polymorphism (SNP) rs1225537 of the TCF7L2 gene and rs9939609 of the FTO gene polymorphism was performed.

Results. The occurrence and association of genotypes of the FTO and TCF7L2 gene with the components of MS were assessed separately in men and women. In women, the risk allele of the FTO gene was significantly more common among people with abdominal obesity. In males, the risk allele of the FTO gene was associated only with hyperglycemia. In both groups, the risk allele of the TCF7L2 gene was significantly more common in persons with hyperglycemia, while in men, the risk allele of the TCF7L2 gene was also associated with the development of abdominal obesity.

Conclusions. We confirmed the association between the rs9939609 risk allele of the FTO gene with the development of abdominal obesity, as well as the risk allele rs1225537 of the TCF7L2 gene with the development of hyperglycemia in the Russian population. Our study also demonstrated various combinations of components of MS in the group of men and women in carriers of risk alleles s9939609 of the FTO gene and rs1225537 of the TCF7L2 gene.

1. Kontrogianni-Konsantopoulos A, Benian G, Granziet H. Advances in muscle physiology and pathophysiology. J Biomed Biotechnol. 2012;2012:930836. doi:10.n55/2012/930836

2. MartinsAR, Nachbar RT, Gorjao R, Vinolo MA, Festuccia WT, Lambertucci RH et al. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis. 2012;11:30. doi:10.1186/1476-511X-11-30

3. Litvinova LS, Kirienkova EV, Mazunin IO, Vasilenko MA, Fattakhov NS. Insulin resistance pathogenesis in metabolic obesity. Biomedical Chemistry. 2015;61(1):70-82. In Russian. doi:10.18097/PBMC20156101070

4. Wifi MA, Assem M, Elsherif RH, El-Azab HA, Saif A. Tolllike receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot. Medicine (Baltimore). 2017;96(17):e676. doi:10.1097/MD.0000000000006760

5. Taha IM, Abdu Allah AM, Abd El Gayed E. M. Expression of toll-like receptor 4 and its connection with type 2 diabetes mellitus. Cell Mol Biol (Noisy-le-grand). 2018;64(13):15-20.

6. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889-894. doi:10.1126/science.1141634

7. Silbernagel G, Renner W, Grammer TB, Hugl SR, Bertram J, Kleber ME et al. Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagonlike peptide 1. Diabetes Metab Res Rev. 2011;27(5):499-505. doi:10.1002/dmrr.1194

8. Epidemiology of cardiovascular diseases in different regions of Russia (ESSE-RF). The rationale for and design of the study Research organizing committee of the ESSE-RF project. Rus J Prev Med Pub Health. 2013;6:25-34. In Russian.

9. 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; International Association for the Study of Obesity. Circulation. 2009;120 (16):1640-1645. doi:10.1161/CIRCULATTONAHA.109.192644

10. Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169(4):505-514. doi:10.1093/aje/kwn359

11. Livingstone KM, Celis-Morales C, Papandonatos GD, Erar B, Florez JC, Jablonski KA et al. FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials. Br Med J. 2016;354: i4707. doi:10.1136/bmj.i4707

12. Dang LC, Samanez-Larkin GR, Smith CT, Castrellon JJ, Perkins SF, Cowan RL et al. FTO affects food cravings and interacts with age to influence age-related decline in food cravings. Physiol Behav. 2018;192:188-193. doi:10.1016/j.physbeh.2017.12.013

13. Jin T. Current understanding on role of the Wnt signaling pathway effector TCF7L2 in glucose homeostasis. Endocr Rev. 2016;37(3):254-277. doi:10.1210/er.2015-1146

14. Khromova NV, Rotar’ OP, Erina AM, Shavshin DA, Alekseeva NP, Kostareva AA et al. Relationship rs9939609 polymorphism of FTO gene with metabolic syndrome and its components in Russian population. Arterial’ naya Gipertenziya = Arterial Hypertension. 2013;19(4): 311-319. doi. org:10.18705/1607-419X-2013-19-4-311-319

15. In Russian]. dbSNP. Available from: https://www.ncbi.nlm. nih.gov/snp/rs9939609

16. Khromova NV, Rotar’ OP, Dudorova EA, Kolesova EP, Moguchaya EV, Boyarinova MA et al. Is 122537 TCF7L2 gene polymorphism — genetic marker of metabolic syndrome or only its components? Translat Med. 2014;3:82-87. In Russian.

17. Silbernagel G, Renner W, Grammer TD, Hugl SR, Bertram J, Kleber ME et al. Association of TCF7L2 SNPs with age at onset of type 2 diabetes and proinsulin/insulin ratio but not with glucagon-like peptide 1. Diabetes Metab Res Rev. 2011;27(5):499-505. doi.org/10.1002/dmrr.1194.

18. Stolerman ES, Manning AK, McAteer JB, Fox CS, Dupuis J, Meigs JB et al. TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study. Diabetologia. 2009;52(4):614-620. doi:10. 1007/s00125-009-1266-2