Investigation of the association of AGTR1 A1166C rs5186 and FTO rs9939609 polymorphisms with the obesity in children and adolescents
Keywords:AGTR1 A1166C (rs5186), Children and adolescents, FTO rs9939609, Obesity, Polymorphism
Obesity is a risk factor for a number of chronic conditions. Obesity is clinically defined using the body mass index (BMI) as weight in kg divided by (height)2 in m2 correlated with obesity. Currently, genetic markers of obesity are being studied. This study focused on the association between the angiotensin II receptor AGTR1 gene (A1166C) and fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase (FTO) (rs9939609) in obese children and adolescents patients in Rostov region, Russia. Five-hundreds of Russian nationality child and adolescent were recruited for the obesity-control studies. The relationship between the A1166C polymorphism of the AGTR1 gene in 300 children and adolescents included as the unhealthy group, compared with healthy group of 200 participants were investigated. Genotyping of A1166C polymorphisms of the AGTR1 rs5186 gene was performed using PCR allele-specific primers. Polymorphisms of the AGTR1 A1166C (rs5186) genes in donor DNA samples were typed by the electrophoretic method using commercial test systems from the Lytech research and production company. The relationship between obesity and AGTR1 gene polymorphism (A1166C) was not established between the obesity and control groups in terms of the frequency of occurrence of the CC genotype (P = 1.000) and (OR 1.05; 95% CI (0.53 – 2.10)) and the C allele (P = 0.942) and (OR 1.01; 95% CI (0.76 – 1.35)). However, in the occurrence of frequency genotype of AA (P = 0.003; OR 0.57; 95% CI (0.39 – 0.82)) and T (P = 0.006) of allele and (OR 1.44; 95% CI (1.11 – 1.87)) the rs9939609 of the FTO gene were revealed differences (P <0.05) between patients and control groups. The association between genotypes obesity risk was indicated, and a significant relationship was shown between the occurrence of obesity with the FTO rs9939609 polymorphism.
Published Online First 20/5/2022
Gregg EW, Shaw JE. Global health effects of overweight and obesity. N Engl J Med. 2017; 377:80-81. DOI: 10.1056/NEJMe1706095
Bray GA, Bellanger T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine. 2006;29(1):109–17. DOI: 10.1385/ENDO:29:1:109
Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al. 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): 2627–42. DOI: 10.1016/S0140-6736(17)32129-3
Simmonds M, Llewellyn A, Owen CG, Woolacott N. Predicting adult obesity from childhood obesity: a systematic review and meta‐analysis. Obes Rev. 2016; 17(2): 95–107. DOI: 10.1111/obr.12334
Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. C R Biol. 2017; 340(2): 87–108. DOI: 10.1016/j.crvi.2016.11.007
Yang Q, Xiao T, Guo J, Su Z. Complex relationship between obesity and the fat mass and obesity locus. Int J Biol Sci. 2017; 13(5): 615–29. DOI: 10.7150/ijbs.17051
Salman EM, Hasan BF. The effect of obesity and Insulin Resistance on Liver Enzymes in Type2 Diabetes Mellitus. Baghdad Sci J. 2015; 12(3): 536-545.
Xu X, Zeng H, Xiao D, Zhou H, Liu Z. Genome wide association study of obesity. Zhong Nan Da Xue Xue Bao Yi Xue Ban. (J. Cent. South Univ. Med. Sci). 2013;38(1):95–100. DOI: 10.3969/j.issn.1672-7347.2013.01.018
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538): 197–206. DOI: 10.1038/nature14177
da Silva TER, Andrade NL, de Oliveira Cunha D, Leão-Cordeiro JAB, Vilanova-Costa CAST, Silva AMTC. The FTO rs9939609 polymorphism and obesity risk in teens: Evidence-based meta-analysis. Obes Res Clin Pract. 2018; 12(5): 432–7. DOI: 10.1016/j.orcp.2018.08.001
Shahid SU, Rehman A, Hasnain S. Role of a common variant of Fat Mass and Obesity associated (FTO) gene in obesity and coronary artery disease in subjects from Punjab, Pakistan: a case control study. Lipids Health Dis. 2016;15(1):29. DOI: 10.1186/s12944-016-0200-0
Quan LL, Wang H, Tian Y, Mu X, Zhang Y, Tao K. Association of fat-mass and obesity-associated gene FTO rs9939609 polymorphism with the risk of obesity among children and adolescents: a meta-analysis. Eur Rev Med Pharmacol Sci. 2015; 19(4): 614–23.
Huang X, Zhao J, Yang M, Li M, Zheng J. Association between FTO gene polymorphism (rs9939609 T/A) and cancer risk: a meta‐analysis. Eur J Cancer Care (Engl). 2017; 26(5): e12464. DOI: 10.1111/ecc.12464
Liu AL, Xie HJ, Xie HY, Liu J, Yin J, Hu JS, et al. Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis. BMC Med Genet. 2017; 18(1): 1–7. DOI: 10.1186/s12881-017-0452-1
Ibraheem QA, Al Obaidy LHA, Nasir GA, Al-Obaidi MTM. Fat Mass and Obesity Association gene Polymorphism in PCOS Iraqi Women. Baghdad Sci J. 2020; 17(3 (Suppl.)): 1103. DOI: 10.21123/bsj.2020.17.3(Suppl.).1103
Wrzosek M, Zakrzewska A, Ruczko L, Jabłonowska-Lietz B, Nowicka G. Association between rs9930506 polymorphism of the fat mass & obesity-associated (FTO) gene & onset of obesity in Polish adults. Indian J Med Res. 2016; 143(3): 281. DOI: 10.4103/0971-5916.182617
Khan SM, Chehadeh SEH, Abdulrahman M, Osman W, Al Safar H. Establishing a genetic link between FTO and VDR gene polymorphisms and obesity in the Emirati population. BMC Med Genet. 2018; 19(1): 1–9. DOI: 10.1186/s12881-018-0522-z
Moselhy SS, Alhetari YA, Iyer A, Huwait EA, Al-Ghamdi MA, Al-Ghamdi S, et al. Analysis of SNPs of MC4R, GNB3 and FTO gene polymorphism in obese Saudi subjects. Afr Health Sci. 2017 Dec; 17(4): 1059–69. DOI: 10.4314/ahs.v17i4.14
Ningombam SS, Chhungi V, Newmei MK, Rajkumari S, Devi NK, Mondal PR, et al. Differential distribution and association of FTO rs9939609 gene polymorphism with obesity: A cross-sectional study among two tribal populations of India with East-Asian ancestry. Gene. 2018; 647: 198–204. DOI: 10.1016/j.gene.2018.01.009
Zhu Y, Zhu Y, Lu N, Wang M, Wang Y, Yao T. Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling. Clin Exp Pharmacol Physiol. 2003;30(12):911–8. DOI:10.1111/j.1440-1681.2003.03942.x
Rosenthal T, Gavras I. Angiotensin inhibition and malignancies: a review. J Hum Hypertens. 2009; 23(10): 623–35. DOI: 10.1038/jhh.2009.21
Poirier O, Georges J-L, Ricard S, Arveiler D, Ruidavets J-B, Luc G, et al. New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. J Hypertens. 1998; 16(10): 1443–7. DOI: 10.1097/00004872-199816100-00007.
Musso G, Saba F, Cassader M, Paschetta E, De Michieli F, Pinach S, et al. Angiotensin II type 1 receptor rs5186 gene variant predicts incident NAFLD and associated hypertension: Role of dietary fat-induced pro-inflammatory cell activation. Am J Gastroenterol. 2019; 114(4): 607–19. DOI: 10.14309/ajg.0000000000000154
Simonyte S, Kuciene R, Medzioniene J, Dulskiene V, Lesauskaite V. Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents. BMC Med Genet. 2017; 18(1): 1–9. DOI: 10.1186/s12881-017-0462-z
Mulerova TA, Morozova NI, Maksimov VN, Ogarkov MY. Polymorphism of genes-candidates of renin-angiotensin-aldosteronovy system (ACE, AGT, AGTR1) and effectiveness of treatment of arterial hypertension. Results of research in Mountain Shoria. Syst Hypertens. 2020; 17(4): 49–54. DOI: 10.26442/2075082X.2020.4.200034
Giacchetti G, Faloia E, Sardu C, Mariniello B, Garrapa GGM, Gatti C, et al. Gene expression of angiotensinogen in adipose tissue of obese patients. Int J Obes Relat Metab Disord. 2000 Jun; 24 Suppl 2: S142-3. DOI: 10.1038/sj.ijo.0801305.
Rasha F, Ramalingam L, Gollahon L, Rahman RL, Rahman SM, Menikdiwela K, et al. Mechanisms linking the renin-angiotensin system, obesity, and breast cancer. Endocr Relat Cancer. 2019; 26(12): R653–72. DOI: 10.1530/ERC-19-0314
Procopciuc LM, Sitar-Tăut A, Pop D, Sitar-Tăut D-A, Olteanu I, Zdrenghea D. Renin angiotensin system polymorphisms in patients with metabolic syndrome (MetS). Eur J Intern Med. 2010; 21(5): 414–8. DOI: 10.1016/j.ejim.2010.06.001
Jassim AN, Abd-Alwahab S. Assessment of Inflammasome Activity in Type 2 Diabetes Mellitus and Simple Obesity: Comparative Study. Baghdad Sci J. 2013; 10(4): 1144–49.
Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene–gene and gene–environment interactions. Bioinformatics. 2003; 19(3): 376–82. DOI: 10.1093/ Bioinform. /btf869
Relethford JH. Hardy–weinberg equilibrium. Hum Popul Genet. 2012; 23–48. https://www.wiley.com/en-us/Human+Population+Genetics-p-9780470464670
Abramson JH. WINPEPI updated: computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov. 2011; 8(1): 1. DOI: 10.1186/1742-5573-8-1
Kern PA, Ong JM, Saffari B, Carty J. The effects of weight loss on the activity and expression of adipose-tissue lipoprotein lipase in very obese humans. N Engl J Med. 1990; 322(15): 1053–9. DOI: 10.1056/NEJM199004123221506
Djalalinia S, Qorbani M, Peykari N, Kelishadi R. Health impacts of obesity. Pakistan J Med Sci. 2015; 31(1): 239. DOI: 10.12669/pjms.311.7033
Li X, Wu N, Ji H, Huang Y, Hu H, Li J, et al. A male-specific association between AGTR1 hypermethylation and coronary heart disease. Bosn J basic Med Sci. 2020; 20(1): 31. DOI: 10.17305/bjbms.2019.4321
Ali EMM, Diab T, Elsaid A, Abd El Daim HA, Elshazli RM, Settin A. Fat mass and obesity-associated (FTO) and leptin receptor (LEPR) gene polymorphisms in Egyptian obese subjects. Arch Physiol Biochem. 2021; 127(1): 28–36. DOI: 10.1080/13813455.2019.1573841
Prakash J, Mittal B, Srivastava A, Awasthi S, Srivastava N. Association of FTO rs9939609 SNP with obesity and obesity-associated phenotypes in a North Indian population. Oman Med J. 2016; 31(2): 99. DOI: 10.5001/omj.2016.20
Batubara JRL. Association of fat mass and obesity-associated gene (FTO) rs9939609 variant with early onset obesity among Bataknese and Chinese children in Indonesia: a case-control study. Indones Biomed J. 2017; 9(3): 147–52. DOI: 10.18585/inabj.v9i3.322
Zhao N-N, Dong G-P, Wu W, Wang J-L, Ullah R, Fu J-F. FTO gene polymorphisms and obesity risk in Chinese population: a meta-analysis. Springer; 2019. DOI: 10.1007/s12519-019-00254-2
Wiemerslage L, Nilsson EK, Solstrand Dahlberg L, Ence‐Eriksson F, Castillo S, Larsen AL, et al. An obesity‐associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images. Eur J Neurosci. 2016; 43(9): 1173–80. DOI: 10.1111/ejn.13177
Manco L, Pinho S, Albuquerque D, Machado‐Rodrigues AM, Padez C. Physical activity and the association between the FTO rs9939609 polymorphism and obesity in Portuguese children aged 3 to 11 years. Am J Hum Biol. 2019; 31(6): e23312. DOI: 10.1002/ajhb.23312
Cho H, Jin H, Eom Y. The interaction between FTO rs9939609 and physical activity is associated with a 2‐fold reduction in the risk of obesity in Korean population. Am J Hum Biol. 2021; 33(3): e23489. DOI: 10.1002/ajhb.23489
Wang D, Wu Z, Zhou J, Zhang X. Rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene and metabolic syndrome susceptibility in the Chinese population: a meta-analysis. Endocrine. 2020; 1–8. DOI:10.1007/s12020-020-02280-x
Abd Ali AH, Shkurat TP, Abbas AH. Association analysis of FTO gene polymorphisms rs9939609 and obesity risk among the adults: A systematic review and meta-analysis. Meta Gene. 2020; 100832. DOI: 10.1016/j.mgene.2020.100832
Oyeyemi BF, Ologunde CA, Olaoye AB, Alamukii NA. FTO gene associates and interacts with obesity risk, physical activity, energy intake, and time spent sitting: pilot study in a Nigerian population. J Obes. 2017; 2017. DOI: 10.1155/2017/3245270
Huđek A, Škara L, Smolkovič B, Kazazić S, Ravlić S, Nanić L, et al. Higher prevalence of FTO gene risk genotypes AA rs9939609, CC rs1421085, and GG rs17817449 and saliva containing Staphylococcus aureus in obese women in Croatia. Nutr Res. 2018; 50: 94–103. DOI: 10.1016/j.nutres.2017.12.005
Abd El-Aziz TA, Mohamed RH, Rezk NA. Association of angiotensin II type I and type II receptor genes polymorphisms with the presence of premature coronary disease and metabolic syndrome. Mol Biol Rep. 2014; 41(2): 1027–33. DOI: 10.1007/s11033-013-2947-y
Mehri S, Mahjoub S, Hammami S, Zaroui A, Frih A, Betbout F, et al. Renin-angiotensin system polymorphisms in relation to hypertension status and obesity in a Tunisian population. Mol Biol Rep. 2012; 39(4): 4059–65. DOI: 10.1007/s11033-011-1187-2
Razbekova M, Issanov A, Chan M-Y, Chan R, Yerezhepov D, Kozhamkulov U, et al. Genetic factors associated with obesity risks in a Kazakhstani population. BMJ Nutr Prev Heal. 2021; bmjnph-2020. DOI: 10.1136/bmjnph-2020-000139
Pacholczyk M, Ferenc T, Kowalski J, Adamczyk P, Chojnowski J, Ponikowska I. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals. DNA Cell Biol. 2013; 32(8): 435–42. DOI: 10.1089/dna.2013.2014
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