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Polymorphism of PPARG (P12A), APOA1 (G75A), and APOE (C112A and A158C) Genes in Children with Obesity and Arterial Hypertension: A Case-Control Study

https://doi.org/10.15690/vsp.v17i4.1924

Abstract

Background. The genetic nature of a comorbid development of obesity and arterial hypertension (AH) in children is poorly studied. In this regard, it is important to study genes, the polymorphism of which is associated with disturbances in both metabolic processes and control of arterial pressure. Objective. Our aim was to study the association of polymorphisms P12A (rs1801282) of the PPARG gene, G75A (rs670) of the apolipoprotein A1 gene (APOA1), C112A (rs429358) and A158C (rs7412) of the apolipoprotein E gene (APOE) with the development of obesity and AH in children. Methods. The study included children with obesity and AH (case) and healthy children (control) aged from 10 to 17 years. Gene polymorphism was studied by polymerase chain reaction in real time. We determined blood concentrations of cholesterol and its fractions, triglycerides, apoA1, apoB, fasting glucose and glucose tolerance test for all children. Results. Groups of patients with obesity and AH (n = 69) and healthy children (n = 49) were comparable by age and sex. In the case group, there were more carriers of the A allele (25 versus 9% in the healthy group; p = 0.002) and the AA genotype (13% and 2%, respectively; df = 2, p = 0.031) of APOE C112A polymorphism. PPARG and APOA1 polymorphisms as well as APOE A158C polymorphism were not associated with the development of obesity and AH in children. The carriers of the APOE e2 allele had lower concentrations of low density lipoproteins and apoB in the blood; the carriers of the PPARG G allele had lower glycemia values, and the carriers of the A allele of APOA1 G75A polymorphism had higher glycemia values. Conclusion. The APOE C112A polymorphism is associated with a comorbid development of obesity and AH in children. The pathogenetic significance of PPARG and APOA1 polymorphisms warrants further investigation.

About the Authors

Olga P. Kovtun
Ural State Medical University
Russian Federation
Yekaterinburg
Disclosure of interest:

Not declared



Margarita A. Ustyuzhanina
Ural State Medical University
Russian Federation
Yekaterinburg
Disclosure of interest:

Not declared



References

1. Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes. 2006;1(1):11–25. doi: 10.1080/17477160600586747.

2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass 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):2627–2642. doi: 10.1016/S01406736(17)32129-3.

3. Gurova MM. Epidemiology of obesity in children at the modern stage. Problems of pediatric nutritiology. 2014;12(3):36–45. (In Russ).

4. Tutel’yan VA, Baturin AK, Kon’ IYa, et al. Rasprostranennost’ ozhireniya i izbytochnoi massy tela sredi detskogo naseleniya RF: mul’titsentrovoe issledovanie. Pediatriia. 2014;93(5):28–33. (In Russ).

5. Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: a systematic review and metaanalysis. Obes Rev. 2015;17(2):95–107. doi: 10.1111/obr.12334.

6. Pavlovskaya EV, Bagaeva ME, Surkov AG, et al. Obesity in children: diagnostic criteria and clinical manifestations. Problems of pediatric nutritiology. 2012;10(3):18–22. (In Russ).

7. Herouvi D, Karanasios E, Karayianni C, Karavanaki K. Cardio vascular disease in childhood: the role of obesity. Eur J Pediatr. 2013; 172(6):721–732. doi: 10.1007/s00431-013-1932-8.

8. Bolotova NV, Posokhova NV, Dronova EG, et al. Faktory riska formirovaniya arterial’noi gipertenzii u detei i podrostkov s ozhireniem. Pediatriia. 2013;92(5):40–44. (In Russ).

9. Scherbakova MYu, Sinitsyn PA, Poryadina GI, et al. Genetic foundations of metabolic disorders formation in children with obesity. Bulletin of RSMU. 2011;(4):26–31. (In Russ).

10. Ushakova SA, Petrushina AD, Kulichenko MP, et al. Circulating markers of endothelial dysfunction in adolescents with arterial hypertension associated with overweight and obesity. Meditsinskaya nauka i obrazovanie Urala. 2015;8(84):50–54. (In Russ).

11. Kozhevnikova OV, Namazova-Baranova LS, Mytnikova YuS, et al. Obesity and sleep disturbance in children. Pediatric pharmacology. 2016;13(6): 571–576. (In Russ). doi: 10.15690/pf.v13i6.1671.

12. Novikova VP, Eglit AE. Bronchial asthma and obesity in children. Problems of pediatric nutritiology. 2014;12(3):46–51. (In Russ).

13. Anderson AD, Solorzano CM, McCartney CR. Childhood obesity and its impact on the development of adolescent PCOS. Seminars in Reproductive Medicine. 2014;32(03):202–213. doi: 10.1055/s0034-1371092.

14. Bhadoria A, Sahoo K, Sahoo B, et al. Childhood obesity: causes and consequences. J Family Med Prim Care. 2015;4(2):187–192. doi: 10.4103/2249-4863.154628.

15. who.int [Internet]. Non communicable diseases. World Health Organization. 2017 [cited 2018 May 17]. Available from: http:// www.who.int/mediacentre/factsheets/fs355/en/.

16. Barbieri M, Desesquelles A, Egidi V, et al. Obesity-related mortality in France, Italy, and the United States: a comparison using multiple cause-of-death analysis. Int J Public Health. 2017;62(6):623–629. doi: 10.1007/s00038-017-0978-1.

17. Shcherbakova MYu, Poryadina GI, Kovaleva EA Problema ozhireniya v detskom vozraste. Eksp Klin Gastroenterol. 2010;(7):74–82. (In Russ).

18. van Vliet M, Heymans M, von Rosenstiel I, et al. Cardiometabolic risk variables in overweight and obese children: a worldwide comparison. Cardiovasc Diabetol. 2011;10(1):106. doi: 10.1186/ 1475-2840-10-106.

19. Herrera B, Lindgren C. The genetics of obesity. Curr Diab Rep. 2010;10(6):498–505. doi: 10.1007/s11892-010-0153-z.

20. Vimaleswaran K, Tachmazidou I, Zhao J, et al. Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI. Hum Mol Genet. 2012;21(20):4537–4542. doi: 10.1093/hmg/dds283.

21. Pihlajamaki J, Schwab U, Kaminska D, et al. Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial. Genes Nutr. 2015;10(6):43. doi: 10.1007/s12263-015-0493-z.

22. Gomez P, Perez-Martinez P, Marin C, et al. APOA1 and APOA4 gene polymorphisms influence the effects of dietary fat on LDL particle size and oxidation in healthy young adults. J Nutr. 2010;140(4):773–778. doi: 10.3945/jn.109.115964.

23. Olano-Martin E, Anil E, Caslake M, et al. Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDLcholesterol response to fish oil. Atherosclerosis. 2010;209(1): 104–110. doi: 10.1016/j.atherosclerosis.2009.08.024.

24. Ordovas JM. Apolipoprotein E isoform phenotyping methodology and population frequency with identification of apoE1 and apoE5 isoforms. J Lipid Res. 1987;28(4):371–380.

25. Phillips M. Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014;66(9):616–623. doi: 10.1002/iub.1314.

26. Niu W, Qi Y, Qian Y, 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):1060–1066. doi: 10.1038/hr.2009.164.

27. 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): 245–255. doi: 10.1038/jhh.2012.37.

28. Lamri A, Abi Khalil C, Jaziri R, et al. Dietary fat intake and polymorphisms at the PPARG locus modulate BMI and type 2 diabetes risk in the D.E.S.I.R. prospective study. Int J Obes (Lond). 2011;36(2):218–224. doi: 10.1038/ijo.2011.91.

29. Juo S, Wyszynski D, Beaty T, et al. Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am J Med Genet. 1999;82(3):235–241. doi: 10.1002/(sici)1096-8628(19990129)82:3<235::aid-ajmg8>3.3.co;2-8.

30. Federal’nye klinicheskie rekomendatsii (protokoly) po vedeniyu detei s endokrinnymi zabolevaniyami. Ed by Dedov II, Peterkova VA. Moscow: Praktika; 2014. pp. 164–182. (In Russ).

31. Aleksandrov AA, Kislyak OA, Leont’eva IV, Rozanov VB. Diagnostika, lechenie i profilaktika arterial’noi gipertenzii u detei i podrostkov. Rossiiskie rekomendatsii (vtoroi peresmotr). Cardiovascular therapy and prevention. 2009; 8(4 Suppl 1):1–32. (In Russ).

32. Order of the Ministry of Health of the Russian Federation № 621 «O kompleksnoi otsenke sostoyaniya zdorov’ya detei» dated December 30, 2003. (In Russ). http://www.consultant.ru/document/cons_doc_LAW_126812/

33. who.int http://www.who.int/topics/physical_ activity/physical-activity-final.pdf.

34. Eichner JE, Dunn ST, Perveen G, et al. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002;155(6):487–495. doi: 10.1093/aje/155.6.487.

35. Horita N, Kaneko T. Genetic model selection for a case-control study and a meta-analysis. Meta Gene. 2015;5:1–8. doi: 10.1016/j.mgene.2015.04.003.

36. Kalyuzhnaya OV. Vklad genov lipidotransportnoi sistemy v formirovanie narushenii lipidnogo obmena u podrostkov s essentsial’noi arterial’noi gipertenziei. [dissertation abstract] Irkutsk; 2016. 22 p. (In Russ). http://www.fesmu.ru/elib/Book.aspx?id=172704

37. Bhatt S, Misra A, Sharma M, et al. Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-_2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol Ther. 2012;14(9):828–834. doi: 10.1089/dia.2011.0277.

38. Morini E, Tassi V, Capponi D, et al. Interaction between PPARgamma2 variants and gender on the modulation of body weight. Obesity (Silver Spring). 2008;16(6):1467–1470. doi: 10.1038/oby.2008.225.

39. Auwerx J. PPAR_, the ultimate thrifty gene. Diabetologia. 1999; 42(9):1033–1049. doi: 10.1007/s001250051268.

40. Wang X, Liu J, Ouyang Y, et al. The association between the Pro12Ala variant in the PPAR_2 gene and type 2 diabetes mellitus and obesity in a Chinese population. PLoS One. 2013;8(8):e71985. doi: 10.1371/journal.pone.0071985.

41. Mehrad-Majd H, Ghayour-Mobarhan M, Zali M. Effect of two common variants in PPAR-_2 gene on susceptibility to obesity. Biomed Res (Aligarh). 2017;28(13):5671–5677.

42. Munoz-Yanez C, Perez-Morales R, Moreno-Macias H, et al. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children. Genet Mol Biol. 2016; 39(4):54–553. doi: 10.1590/1678-4685-gmb-2015-0267.

43. Meirhaeghe A, Tanck M, Fajas L, et al. Study of a new PPAR_2 promoter polymorphism and haplotype analysis in a French population. Mol Genet Metab. 2005;85(2):140–148. doi: 10.1016/j.ymgme.2005.02.004.

44. Lagou V, Scott R, Manios Y, et al. Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study. Obesity (Silver Spring). 2008;16(4):913–918. doi: 10.1038/oby.2008.1.

45. Kypreos KE, Li X, van Dijk KW, et al. Molecular mechanisms of type III hyperlipoproteinemia: The contribution of the carboxyterminal domain of ApoE can account for the dyslipidemia that is associated with the E2/E2 phenotype. Biochemistry. 2003;42(33): 9841–9853. doi: 10.1021/bi0271796.

46. Kypreos K, Karagiannides I, Fotiadou E, et al. Mechanisms of obesity and related pathologies: role of apolipoprotein E in the development of obesity. FEBS Journal. 2009;276(20):5720–5728. doi: 10.1111/j.1742-4658.2009.07301.x.

47. Arbones-Mainar J, Johnson L, Altenburg M, Maeda N. Differential modulation of diet-induced obesity and adipocyte functionality by human apolipoprotein E3 and E4 in mice. Int J Obes (Lond). 2008;32(10):1595–1605. doi: 10.1038/ijo.2008.143.

48. Volcik K, Barkley R, Hutchinson R, et al. Apolipoprotein E polymorphisms predict low density lipoprotein cholesterol levels and carotid artery wall thickness but not incident coronary heart disease in 12,491 ARIC study participants. Am J Epidemiol. 2006; 164(4):342–348. doi: 10.1093/aje/kwj202.

49. Oh JY, Barrett-Connor E; Rancho Bernardo Study Group. Apolipoprotein E polymorphism and lipid levels differ by gender and family history of diabetes: the Rancho Bernardo Study. Clin Genet. 2008;60(2):132–137. doi: 10.1034/j.1399-0004.2001.600207.x.

50. Calderon-Garciduenas L, Jewells V, Galaz-Montoya C, et al. Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City. Environ Res. 2016;150:411–422. doi: 10.1016/j.envres.2016.06.026.

51. Elosua R, Demissie S, Cupples L, et al. Obesity modulates the association among APOE genotype, insulin, and glucose in men. Obes Res. 2003;11(12):1502–1508. doi: 10.1038/oby.2003.201.

52. Fulton J, Dai S, Grunbaum J, et al. Apolipoprotein E affects serial changes in total and low-density lipoprotein cholesterol in adolescent girls: Project Heart Beat. Metabolism. 1999;48(3): 285–290. doi: 10.1016/s0026-0495(99)90073-2.

53. Callas N, Poveda E, Baracaldo C. [Genetic polymorphism of the E apolipoprotein in school age children: comparison with levels of plasma lipids and apolipoproteins. (In Spanish).] Biomedica. 2007;27(4):526–536.

54. Smart M, Dedoussis G, Louizou E, 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.

55. Toptas B, Gormus U, Ergen A, et al. Comparison of lipid profiles with APOA1 MspI polymorphism in obese children with hyperlipidemia. In Vivo. 2011;25(3):425–430.

56. Kendysh IN. Regulyatsiya uglevodnogo obmena. Moscow: Meditsina; 1985. (In Russ).


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For citations:


Kovtun O.P., Ustyuzhanina M.A. 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):307-315. https://doi.org/10.15690/vsp.v17i4.1924

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