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The Significance of Genetic Marker Studies in the Treatment and Prevention of Obesity in Children and Adolescents

https://doi.org/10.31550/1727-2378-2024-23-3-67-72

Abstract

Aim. To consider the role of hereditary predisposition in the formation of obesity, and to analyze the importance of genetic marker studies in the treatment and prevention of obesity in children and adolescents.

Key points. The increasing prevalence of obesity among children and adolescents over the past decades is one of the most important medical and social problems, since obesity contributes to the emergence of such non-infectious diseases as type 2 diabetes mellitus and arterial hypertension, which are rightly considered a non-infectious epidemic of the 21st century. At the same time, the role of hereditary predisposition in the formation of obesity is well known, and therefore the search for its genetic markers becomes relevant.

Conclusion. Genetic markers help not only to identify patients at risk for obesity, but also to diagnose metabolic disorders at early stages: dyslipidaemia, disorders of carbohydrate metabolism, early manifestations of endothelial dysfunction, which will help to prevent the development of heart attacks, strokes, type 2 diabetes mellitus, and thus reduce disability and mortality from non-infectious diseases. Along with this, the isolation of certain genetic markers and their combinations will allow the creation of personalized obesity treatment and prevention programs.

About the Authors

O. V. Peresetskaya
Smolensk State Medical University
Russian Federation

28 Krupskaya Str., Smolensk,  214019



L. V. Kozlova
Smolensk Regional Children's Clinical Hospital
Russian Federation

30B Marshal Konev Str., Smolensk, 214019



V. I. Larionova
North-Western State Medical University named after I.I. Mechnikov
Russian Federation

41 Kirochnaya Str., Saint Petersburg, 191015



References

1. Gritsinskaya V., Novikova V. Obesity in children in the regions of Russia. Российский педиатрический журнал (Russian Pediatric Journal). 2021;2(3):39. (in English). DOI: 10.1136/archdischild-2021-europaediatrics.205

2. Gurova M.M. Epidemiology of obesity in children at the modern stage. Pediatric Nutrition. 2014;12(3):36–45. (in Russian)

3. Gritsinskaya V.L., Novikova V.P., Khavkin A.I. Epidemiology of obesity in children and adolescents (systematic review and meta-analysis of publications over a 15-year period). Clinical Practice in Pediatrics. 2022;17(2):126–35. (in Russian). DOI: 10.20953/1817-7646-2022-2-126-135

4. Bradfield J.P., Vogelezang S., Felix J.F., Chesi A. et al. A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity. Hum. Mol. Genet. 2019;28(19):3327–38. DOI: 10.1093/hmg/ddz161

5. Panera N., Mandato C., Crudele A., Bertrando S. et al. Genetics, epigenetics and transgenerational transmission of obesity in children. Front. Endocrinol. 2022;13:1006008. DOI: 10.3389/fendo.2022.1006008

6. Vourdoumpa A., Paltoglou G., Charmandari E. The genetic basis of childhood obesity: a systematic review. Nutrients. 2023;15(6):1416. DOI: 10.3390/nu15061416

7. Littleton S.H., Berkowitz R.I., Grant S.F.A. Genetic determinants of childhood obesity. Mol. Diagn. Ther. 2020;24(6):653–63. DOI: 10.1007/s40291-020-00496-1

8. Dashti H.S., Miranda N., Cade B.E., Huang T. et al. Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank. BMC Med. 2022;20(1):5. DOI: 10.1186/s12916-021-02198-9

9. King S.E., Skinner M.K. Epigenetic transgenerational inheritance of obesity susceptibility. Trends Endocrinol. Metab. 2020;31(7):478–94. DOI: 10.1016/j.tem.2020.02.009

10. Huang R.C., Melton P.E., Burton M.A., Beilin L.J. et al. Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors. Epigenetics. 2022;17(8):819–36. DOI: 10.1080/15592294.2021.1876297

11. Loos R.J.F., Yeo G.S.H. The genetics of obesity: from discovery to biology. Nat. Rev. Genet. 2022;23(2):120–33. DOI: 10.1038/s41576-021-00414-z

12. Mahmoud R., Kimonis V., Butler M.G. Genetics of obesity in humans: a clinical review. Int. J. Mol. Sci. 2022;23(19):11005. DOI: 10.3390/ijms231911005

13. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in bodymass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627–42. DOI: 10.1016/S0140-6736(17)32129-3

14. Bairqdar A., Shakhtshneider E., Ivanoshchuk D., Mikhailova S. et al Rare variants of obesity-associated genes in young adults with abdominal obesity. J. Pers. Med. 2023;13(10):1500. DOI: 10.3390/jpm13101500

15. West N.R., Dorling J., Thackray A.E., Hanson N.C. et al. Effect of obesity-linked FTO rs9939609 variant on physical activity and dietary patterns in physically active men and women. J. Obes. 2018;2018:7560707. DOI: 10.1155/2018/7560707

16. Berná G., Oliveras-López M.J., Jurado-Ruíz E., Tejedo J. et al. Nutrigenetics and nutrigenomics insights into diabetes etiopathogenesis. Nutrients. 2014;6(11):5338–69. DOI: 10.3390/nu6115338

17. Kovtun O.P., Ustyuzhanina M.A. Molecular-genetic basics formation of obesity and related diseases in children. Medical Science and Education of Ural. 2018;19(1): 48–54. (in Russian)

18. Loos R.J., Yeo G.S. The bigger picture of FTO: the first GWAS-identified obesity gene. Nat. Rev. Endocrinol. 2014;10(1):51–61. DOI: 10.1038/nrendo.2013.227

19. Tung Y.C.L., Gulati P., Liu C.-H., Rimmington D. et al. FTO is necessary for the induction of leptin resistance by high-fat feeding. Mol. Metab. 2015;4(4):287–98. DOI: 10.1016/j.molmet.2015.01.011

20. Dastgheib S.A., Bahrami R., Setayesh S., Salari S. et al. Evidence from a meta-analysis for association of MC4R rs17782313 and FTO rs9939609 polymorphisms with susceptibility to obesity in children. Diabetes Metab. Syndr. 2021;15(5):102234. DOI: 10.1016/j.dsx.2021.102234

21. López-Rodríguez G., Estrada-Neria A., Suárez-Diéguez T., Tejero M.E. et al. Common polymorphisms in MC4R and FTO genes are associated with BMI and metabolic indicators in Mexican children: differences by sex and genetic ancestry. Gene. 2020;754:144840. DOI: 10.1016/j.gene.2020.144840

22. Yu K., Li L., Zhang L., Guo L. et al. Association between MC4R rs17782313 genotype and obesity: a meta-analysis. Gene. 2020;733:144372. DOI: 10.1016/j.gene.2020.144372

23. Cataldi S., Costa V., Ciccodicola A., Aprile M. PPARγ and diabetes: beyond the genome and towards personalized medicine. Curr. Diab. Rep. 2021;21(6):18. DOI: 10.1007/s11892-021-01385-5

24. Muntean C., Sasaran M.O., Crisan A., Banescu C. Effects of PPARG and PPARGC1A gene polymorphisms on obesity markers. Front. Public Health. 2022;10:962852. DOI: 10.3389/fpubh.2022.962852

25. Imaizumi T., Ando M., Nakatochi M., Yasuda Y. et al. Effect of dietary energy and polymorphisms in BRAP and GHRL on obesity and metabolic traits. Obes. Res. Clin. Pract. 2018;12(suppl.2):S39–48. DOI: 10.1016/j.orcp.2016.05.004

26. Borodina S.V., Gapparova K.M., Zainudinov Z.M., Grigorian O.N. Genetic predictors of obesity development. Obesity and Metabolism. 2016;13(2):7–13. (in Russian). DOI: 10.14341/omet201627-13

27. Boyarinova M.A., Rotar O.P., Kostareva A.A., Khromova N.V. et al. Association between the FTO gene rs9939609 polymorphism and metabolic health in obese patients living in St. Petersburg. Doctor.Ru. 2018;8(152):20–4. (in Russian). DOI: 10.31550/1727-2378-2018-152-8-20-24

28. Rotar O.P., Kolesova E.P., Moguchaya E.V., Boyarinova M.A. et al. Genetic markers of the metabolic syndrome in the Russian population (based on the ESSE-RF study). Arterial Hypertension. 2019;25(5):467–77. (in Russian). DOI: 10.18705/1607-419H-2019-25-5-467-477

29. Lapik I.A., Gapparova К.М., Sorokina E.Yu., Grigoryan O.N. The evaluation of the effectiveness of diet therapy for obese patients basing on studying of the polymorphism rs9939609 of the FTO gene. Obesity and Metabolism. 2017;14(4):46–50. (in Russian). DOI: 10.14341/OMET2017446-50

30. Sovio U., Mook-Kanamori D.O., Warrington N.M., Lawrence R. et al. Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: the complex nature of genetic association through growth and development. PLoS Genet. 2011;7(2):e1001307. DOI: 10.1371/journal.pgen.1001307

31. Marakhovskaya T.A., Alaa Hashim A.A., Amelina M.A., Lyangasova O.V. et al. Meta-analysis of the association of polymorphic variants of the FTO, LPL, LIPC, PON1 genes with the risk of obesity in children and adolescents. Live and Bio-Abiotic Systems. 2021;36. (in English). DOI: 10.18522/2308-9709-2021-36-5

32. Alaa Hashim A.A., Bocharova O.V., Shkurat T.P., Shkurat M.A. et al. Association of Ser447Ter polymorphisms of the LPL gene and rs9939609 of the FTO gene with obesity in children and adolescents in the Rostov-on-Don population. Bulletin of Perm University. Biology. 2021;2:119–27. (in Russian). DOI: 10.17072/1994-9952-2021-2-119-127

33. Bairova T.A., Sheneman E.A., Ievleva K.D., Rychkova L.V. Interrelation of rs9939609 polymorphism of the FTO gene with clinical and metabolic parameters in girls with different fat deposition topography: a pilot study. Pediatrics. Journal named after G.N. Speransky. 2021;100(2):211–18. (in Russian)

34. Shahid A., Rana S., Saeed S., Imran M. et al. Common variant of FTO gene, rs9939609, and obesity in Pakistani females. Biomed. Res. Int. 2013;2013:324093. DOI: 10.1155/2013/324093

35. Yang W., Kelly T., He J. Genetic epidemiology of obesity. Epidemiol. Rev. 2007;29:49–61. DOI: 10.1093/epirev/mxm004

36. Sharafetdinov Kh.Kh., Yudochkin A.V., Plotnikova O.A. The role of genetic factors in the development of metabolic syndrome. Nutrition. 2016;6(4):29–35. (in Russian). DOI: 10.20953/2224-5448-2016-4-29-35

37. Khasanova K.B., Medvedeva M.S., Valeeva E.V., Rodygina Zh.A. et al. The role of the rs1801282 PPARG polymorphic marker in the prediction and choice of carbohydrate metabolism disorders management: a review. Consilium Medicum. 2022;24(4):266–70. (in Russian). DOI: 10.26442/20751753.2022.4.201672

38. Lifshits G.I., Kokh N.V., Kireeva V.V., Apartsin K.A. Some molecular genetic mechanisms of the obesity and metabolic syndrome. Pharmacogenetics and Pharmacogenomics. 2017;1:5–9. (in Russian)

39. Kovtun O.P., Ustyuzhanina M.A. Impact of PPARG (Pro12Ala) polymorphism on early debut of obesity in children. Journal of Ural Medical Academic Science. 2018;15(1):42–7. (in Russian). DOI: 10.22138/2500-0918-2018-15-1-42-47

40. Kovtun O.P., Ustyuzhanina М.А. Polymorphism of PPARG (P12A), APOA1 (G75A), and APOE (C112A and A158C) genes in children with obesity and arterial hypertension: a case-control study. Current Pediatrics. 2018;17(4):307–15. (in Russian). DOI: 10.15690/vsp.v17i4.1924

41. Pogozheva A.V., Sorokina E.Yu., Baturin A.K., Peskova E.V. et al The development of diagnostics and alimentary prevention system of noncommunicable diseases. Almanac of Clinical Medicine. 2015;suppl.1:67–74. 42. Neeha V.S., Kinth P. Nutrigenomics research: a review. J. Food Sci. Technol. 2013;50(3):415–28. DOI: 10.1007/s13197-012-0775-z

42. Smart M., Dedoussis G., Louizou E., Yannakoulia M. et al. APOE, CETP and LPL genes show strong association with lipid levels in Greek children. Nutr. Metab. Cardiovasc. Dis. 2010;20(1):26–33. DOI: 10.1016/j.numecd.2009.02.005

43. Phillips M. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014;66(9):616–23. DOI: 10.1002/iub.1314

44. Kypreos K.E., Li X., van Dijk K.W., Havekes L.M. et al. Molecular mechanisms of type III hyperlipoproteinemia: the contribution of the carboxy-terminal domain of ApoE can account for the dyslipidemia that is associated with the E2/E2 phenotype. Biochemistry. 2003;42(33):9841–53. DOI: 10.1021/bi0271796

45. Niu W., Qi Y., Qian Y., Gao P. et al. The relationship between apolipoprotein E е2/е3/е4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls. Hypertens. Res. 2009;32(12): 1060–6. DOI: 10.1038/hr.2009.164

46. Stoumpos S., Hamodrakas S., Anthopoulos P., Bagos P. The association between apolipoprotein E gene polymorphisms and essential hypertension: a meta-analysis of 45 studies including 13 940 cases and 16 364 controls. J. Hum. Hypertens. 2012;27(4): 245–55. DOI: 10.1038/jhh.2012.37

47. Scherbakova M.Yu., Sinitsyn P.A., Poryadina G.I., Khmyrova A.P. et al. Genetic foundations of metabolic disorders formation in children with obesity. Bulletin of Russian State Medical University. 2011;4:26–31. (in Russian)

48. Chubarov T.V., Peterkova V.A., Batischeva G.A., Zhdanova O.A. et al. Characteristics of blood pressure level in children with different body weight. Obesity and Metabolism. 2022;19(1):27–34. (in Russian). DOI: 10.14341/omet12721

49. Kolesnikova I.S., Holyandra I.S., Kushnarenko V.S., Panteleeva N.V. et al. Genetic testing as a tool for obesity prevention and therapy. Therapist’s Bulletin. 2023;3(58). (in Russian). URL: https://journaltherapy.ru/statyi/geneticheskoe-testirovanie-kak-instrument-profilaktiki-i-lechenija-ozhirenija/ (дата обра- щения — 13.02.2024).

50. Valeeva F.V., Medvedeva M.S., Khasanova K.B., Turtseva T.S. et al. Changes in body composition depending on the rs1801282 PPARG polymorphism in patients with different variants of treatment of early carbohydrate metabolism disorders. Medical Herald of the South of Russia. 2021;12(4):27–33. (in Russian). DOI: 10.21886/2219-8075-2021-12-4-27-33

51. Koch N.V., Lifschitz G.I., Voronina E.N. Approaches to the lipid metabolism genes polymorphysm analysis in screening for atherosclerosis risk factors. Russian Journal of Cardiology. 2014;10:53–7. (in Russian). DOI: 10.15829/1560-4071-2014-10-53-057

52. Fatima M.T., Ahmed I., Fakhro K.A., Akil A.S.A. Melanocortin-4 receptor complexity in energy homeostasis, obesity and drug development strategies. Diabetes Obes. Metab. 2022;24(4):583–98. https://doi.org/10.1111/dom.14618

53. Galieva M.O., Troshina Е.А., Mazurina N.V., Artiushin A.V. et al. The role of genetic factors in predicting results of obesity treatment with sibutramine — serotonin-norepinephrine reuptake inhibitor. Obesity and Metabolism. 2016;13(4):21–6. (in Russian). DOI: 10.14341/omet2016421-26


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Peresetskaya O.V., Kozlova L.V., Larionova V.I. The Significance of Genetic Marker Studies in the Treatment and Prevention of Obesity in Children and Adolescents. Title. 2024;23(3):67-72. (In Russ.) https://doi.org/10.31550/1727-2378-2024-23-3-67-72

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