Association between rs8192678 C/T polymorphism of the PPARGC1A gene and metabolically associated fatty liver disease in obese children living in the Moscow region

Over the past 30 years, the incidence of childhood obesity has quadrupled, leading to a rise in metabolically associated fatty liver disease (MAFLD), which has multifactorial genesis. Numerous studies highlight a significant genetic contribution to the development and severity of MAFLD. Purpose of the study. Тo determine the distribution of alleles and genotypes of the rs8192678 C/T polymorphism of the PPARGC1A gene and its relationship with the development of MAFLD in obese children living in the Moscow region. Materials and methods. The study included 87 children with exogenous constitutional obesity. The children were divided into two groups: group I - obesity without MAFLD (n = 43), group II - obesity with MAFLD (n = 44). The association of genotypes with the risk of developing MAFLD was studied in various genetic models. Results. 43 (49.4%) children had genotypes containing the T allele: 4 (4.6%) - homozygous TT genotype, 39 (44.8%) - heterozygous CT genotype. The CC genotype was detected in 44 (50.6%) children. The frequency of allele C was 73%. Carriers of the T allele have almost twice the risk of developing MAFLD than сarriers of the C allele (OR = 2.08 (95% CI: 1.05-4.24), p = 0.041). Conclusion. Тhe rs8192678 polymorphism increases the risk of developing MAFLD already in childhood, and with the homozygous TT genotype, this risk more than doubles. Studying the genetic contribution to the development of MAFLD enables a comprehensive approach to assessing individual risks of each patient.

obesity, children, MAFLD, polymorphism, genotype, PPARGC1A gene

1. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403(10431):1027-1050. doi: 10.1016/S0140-6736(23)02750-2.

2. Savina A. A., Feiginova S. I. Obesity prevalence in population of Russian Federation: before COVID-19 pandemic. Social’nye aspekty zdorov’a naselenia [serial online] 2022;68(5):4. (in Russ.) Available at: http://vestnik.mednet.ru/content/view/1414/30/lang.ru Accessed: 05.05.2024. doi: 10.21045/2071-5021-2022-68-5-4. @@ Савина А. А., Фейгинова С. И. Распространенность ожирения среди населения Российской Федерации: период до пандемии COVID-19. Социальные аспекты здоровья населения [сетевое издание] 2022;68(5):4. Режим доступа: http://vestnik.mednet.ru/content/view/1414/30/lang.ru doi: 10.21045/2071-5021-2022-68-5-4.

3. Dedov I. I., Shestakova M. V., Peterkova V. A. et al. Diabetes mellitus in children and adolescents according to the Federal diabetes registry in the Russian Federation: dynamics of major epidemiological characteristics for 2013-2016. Diabetes mellitus. 2017;20(6):392-402: (In Russ.) doi: 10.14341/DM9460.@@ Дедов И. И., Шестакова М. В., Петеркова В. А. и соавт. Сахарный диабет у детей и подростков по данным Федерального регистра Российской Федерации: динамика основных эпидемиологических характеристик за 2013-2016 гг. Сахарный диабет. 2017;20(6):392-402. doi: 10.14341/DM9460.

4. Mitra S., De A., Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol. 2020;5:16. doi: 10.21037/tgh.2019.09.08.

5. Drozdz D., Alvarez-Pitti J., Wójcik M. et al. Obesity and Cardiometabolic Risk Factors: From Childhood to Adulthood. Nutrients. 2021;13(11):4176. doi: 10.3390/nu13114176.

6. Bokova T. A. Non-alcoholic fatty liver disease in children: relationship with the main components of metabolic syndrome in children. Experimental and Clinical Gastroenterology. 2020;(1):15-20. (In Russ.) doi: 10.31146/1682-8658-ecg-173-1-15-20.@@ Бокова Т. А. Неалкогольная жировая болезнь печени и основные компоненты метаболического синдрома у детей. Экспериментальная и клиническая гастроэнтерология. 2020;(1):15-20. doi: 10.31146/1682-8658-ecg-173-1-15-20.

7. Eslam M., Newsome P. N., Sarin S. K. et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209. doi: 10.1016/j.jhep.2020.03.039.

8. Maev I. V., Andreev D. N., Kucheryavyy Yu. A. Metabolically associated fatty liver disease - a disease of the 21st century. Consilium Medicum. 2022;24(5):15-22. (In Russ.) doi: 10.26442/20751753.2022.5.201532.@@ Маев И. В., Андреев Д. Н., Кучерявый Ю. А. Метаболически ассоциированная жировая болезнь печени - заболевание XXI века. Consilium Medicum. 2022;24(5):325-332. doi: 10.26442/20751753.2022.5.201532.

9. Fernandez-Marcos P. J., Auwerx J. Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr. 2011;93(4):884S-90. doi: 10.3945/ajcn.110.001917.

10. Du F., Yang K. J., Piao L. S. Correlation Between PPARGC1A Gene Rs8192678 G>A Polymorphism and Susceptibility To Type-2 Diabetes. Open Life Sci. 2019;14:43-52. doi: 10.1515/biol-2019-0006.

11. Zhang Y., Li S., Nie H. et al. The rs17782313 polymorphism near MC4R gene confers a high risk of obesity and hyperglycemia, while PGC1α rs8192678 polymorphism is weakly correlated with glucometabolic disorder: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:1210455. doi: 10.3389/fendo.2023.1210455.

12. Zhang R. N., Shen F., Pan Q. et al. PPARGC1A rs8192678 G > A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease. World J Gastroenterol. 2021;27(25):3863-3876. doi: 10.3748/wjg.v27.i25.3863.

13. Peterkova V. A., Bezlepkina O. B., Bolotova N. V. et al. Clinical guidelines «Obesity in children». Problems of Endocrinology. 2021;67(5):67-83. (In Russ.) doi: 10.14341/probl12802.@@ Петеркова В. А., Безлепкина О. Б., Болотова Н. В. и соавт. Клинические рекомендации «Ожирение у детей». Проблемы Эндокринологии. 2021;67(5):67-83. doi: 10.14341/probl12802.

14. Dribnokhodova O. P., Mironov K. O., Korchagin V. I. et al. Characterization of 48 Polymorphic Loci as Potential Markers for the Risk of Ischemic Stroke.Russian Journal of Genetics. 2017;53(6):698-702. (In Russ.) doi: 10.7868/S0016675817060042.@@ Дрибноходова О. П., Миронов К. О., Корчагин В. И. и соавт. Характеристика 48 полиморфных локусов - потенциальных маркеров риска развития ишемического инсульта. Генетика. 2017;53(6): 698-702. doi: 10.7868/S0016675817060042.

15. Mironov K. O., Dunaeva E. A., Dribnokhodova O. P., Shipulin G. A. Opyt ispol’zovaniya sistem geneticheskogo analiza na osnove tekhnologii pirosekvenirovaniya. Spravochnik zaveduyushchego KDL. 2016;(5):33-43. (In Russ.)@@ Миронов К. О., Дунаева Е. А., Дрибноходова О. П., Шипулин Г. А. Опыт использования систем генетического анализа на основе технологии пиросеквенирования. Справочник заведующего КДЛ. 2016;(5):33-43.

16. The R Project for Statistical Computing. Available at: https://www.R-project.org Accessed: 05.05.2024.

17. Aragon T. J., Wollschlaeger D., Omidpanah A. Epitools: Epidemiology Tools [R package epitools version 0.5-10.1] (Electronic resource.) Available at: https://cran.r-project.org/package = epitools Accessed: 05.05.2024.

18. Yoneda M., Hotta K., Nozaki Y. et al. Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol. 2008;8:27. doi: 10.1186/1471-230X-8-27.