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DOI: 10.1055/s-0040-1713154
Association between rs1421085 and rs9939609 Polymorphisms of Fat Mass and Obesity-Associated Gene with High-Density Lipoprotein Cholesterol and Triglyceride in Obese Turkish Children and Adolescents
Abstract
Several studies have shown that rs9939609 and rs1421085 in fat mass and obesity-associated (FTO) gene rs17782313 and rs12970134 in melanocortin-4 receptor (MC4R) gene influence obesity. In the present study, we aimed to determine association between rs9939609, rs1421085, rs17782313, and rs12970134 polymorphism, and their relation with body mass index (BMI), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and lipid values in obese children. We included 100 newly diagnosed obese children and 100 healthy children. The rs1421085 (CC/CT) (p = 0.019) and rs9939609 (AA/AT) (p = 0.002) polymorphism regions were higher in the obese group. Additionally, we found that both the rs1421085 (CC/CT) and rs9939609 (AA/AT) polymorphism associated with high-density lipoprotein cholesterol (p = 0.011 and p = 0.003) and triglycerides (p = 0.01 and p = 0.004) level, respectively. Further, the rs9939609 and rs1421085 variants of FTO gene associated with HDL-cholesterol and triglycerides levels in obese children; however, updated studies with a large sample size are required to establish strong links with genetic variants and risk factors in childhood obesity.
Keywords
childhood obesity - fat mass and obesity gene - high-density lipoprotein cholesterol - melanocortin-4 receptor gene - triglyceridePublikationsverlauf
Eingereicht: 08. April 2020
Angenommen: 04. Mai 2020
Artikel online veröffentlicht:
10. Juni 2020
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References
- 1 Chesi A, Grant SFA. The genetics of pediatric obesity. Trends Endocrinol Metab 2015; 26 (12) 711-721
- 2 Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014; 311 (08) 806-814
- 3 Republic of Turkey, Ministry of Health. General directorate of public health. Accessed September 28, 2019 at: http://beslenme.gov.tr/index.php?lang=tr&page=40
- 4 Ho G, MacKenzie RG. Functional characterization of mutations in melanocortin-4 receptor associated with human obesity. J Biol Chem 1999; 274 (50) 35816-35822
- 5 Gantz I, Miwa H, Konda Y. et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem 1993; 268 (20) 15174-15179
- 6 Huszar D, Lynch CA, Fairchild-Huntress V. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88 (01) 131-141
- 7 Lubrano-Berthelier C, Cavazos M, Dubern B. et al. Molecular genetics of human obesity-associated MC4R mutations. Ann N Y Acad Sci 2003; 994: 49-57
- 8 Srinivasan S, Lubrano-Berthelier C, Govaerts C. et al. Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. J Clin Invest 2004; 114 (08) 1158-1164
- 9 Gulati P, Cheung MK, Antrobus R. et al. Role for the obesity-related FTO gene in the cellular sensing of amino acids. Proc Natl Acad Sci U S A 2013; 110 (07) 2557-2562
- 10 Scuteri A, Sanna S, Chen WM. et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3 (07) e115
- 11 Frayling TM, Timpson NJ, Weedon MN. 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
- 12 Gerken T, Girard CA, Tung YC. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318 (5855): 1469-1472
- 13 Skelton JCR. Overweight and obesity. In: Kliegman R, Nelson WE. eds. Nelson Textbook of Pediatrics. Philadelphia, PA: Saunders; 2007: 232-242
- 14 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28 (07) 412-419
- 15 Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005; 115 (04) e500-e503
- 16 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15 (07) 539-553
- 17 World Health Organization. Commission on ending childhood obesity. Accessed September 27, 2019 at: http://www.who.int/end-childhood-obesity/en/
- 18 Turkish Statistical Institute. İstatistiklerle Çocuk, 2014. Accessed September 27, 2019 at: http://www.tuik.gov.tr/PreHaberBultenleri.do?id=18622
- 19 Solak M, Ozdemir Erdogan M, Yildiz SH. et al. Association of obesity with rs1421085 and rs9939609 polymorphisms of FTO gene. Mol Biol Rep 2014; 41 (11) 7381-7386
- 20 Guclu-Geyik F, Onat A, Yuzbasıogulları AB. et al. Risk of obesity and metabolic syndrome associated with FTO gene variants discloses clinically relevant gender difference among Turks. Mol Biol Rep 2016; 43 (06) 485-494
- 21 Demiralp DO, Berberoglu M, Akar N. Melanocortin-4 receptor polymorphisms in Turkish pediatric obese patients. Clin Appl Thromb Hemost 2011; 17 (01) 70-74
- 22 Tunç S, Demir K, Tükün FA. et al. Melanocortin-4 receptor gene mutations in a group of Turkish obese children and adolescents. J Clin Res Pediatr Endocrinol 2017; 9 (03) 216-221
- 23 Çağlayan AO, Tüysüz B, Coşkun S. et al. A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP. J Hum Genet 2016; 61 (05) 395-403
- 24 Farooqi IS, O'Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 2008; 4 (10) 569-577
- 25 Dwivedi OP, Tabassum R, Chauhan G. et al. Strong influence of variants near MC4R on adiposity in children and adults: a cross-sectional study in Indian population. J Hum Genet 2013; 58 (01) 27-32
- 26 Wang S, Song J, Yang Y, Chawla NV, Ma J, Wang H. Rs12970134 near MC4R is associated with appetite and beverage intake in overweight and obese children: a family-based association study in Chinese population. PLoS One 2017; 12 (05) e0177983
- 27 Vogel CI, Boes T, Reinehr T. et al. Common variants near MC4R: exploring gender effects in overweight and obese children and adolescents participating in a lifestyle intervention. Obes Facts 2011; 4 (01) 67-75
- 28 Fernandes AE, de Melo ME, Fujiwara CT. et al. Associations between a common variant near the MC4R gene and serum triglyceride levels in an obese pediatric cohort. Endocrine 2015; 49 (03) 653-658
- 29 Grant SF, Bradfield JP, Zhang H. et al. Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry. Obesity (Silver Spring) 2009; 17 (07) 1461-1465
- 30 Larder R, Cheung MK, Tung YC, Yeo GS, Coll AP. Where to go with FTO?. Trends Endocrinol Metab 2011; 22 (02) 53-59
- 31 Church C, Moir L, McMurray F. et al. Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 2010; 42 (12) 1086-1092
- 32 Adeyemo A, Chen G, Zhou J. et al. FTO genetic variation and association with obesity in West Africans and African Americans. Diabetes 2010; 59 (06) 1549-1554
- 33 Dina C, Meyre D, Gallina S. et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39 (06) 724-726
- 34 Tan JT, Dorajoo R, Seielstad M. et al. FTO variants are associated with obesity in the Chinese and Malay populations in Singapore. Diabetes 2008; 57 (10) 2851-2857
- 35 Peeters A, Beckers S, Verrijken A. et al. Variants in the FTO gene are associated with common obesity in the Belgian population. Mol Genet Metab 2008; 93 (04) 481-484
- 36 Hess ME, Brüning JC. The fat mass and obesity-associated (FTO) gene: obesity and beyond?. Biochim Biophys Acta 2014; 1842 (10) 2039-2047
- 37 Tanofsky-Kraff M, Han JC, Anandalingam K. et al. The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am J Clin Nutr 2009; 90 (06) 1483-1488
- 38 Timpson NJ, Emmett PM, Frayling TM. et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008; 88 (04) 971-978
- 39 Albuquerque D, Nóbrega C, Manco L. Association of FTO polymorphisms with obesity and obesity-related outcomes in Portuguese children. PLoS One 2013; 8 (01) e54370
- 40 Wang J, Mei H, Chen W. et al. Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty. Int J Obes 2012; 36 (04) 542-547
- 41 Xi B, Shen Y, Zhang M. et al. The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing, China. BMC Med Genet 2010; 11: 107
- 42 Fang H, Li Y, Du S. et al. Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children. BMC Med Genet 2010; 11: 136
- 43 Abdelmajed SS, Youssef M, Zaki ME, Abu-Mandil Hassan N, Ismail S. Association analysis of FTO gene polymorphisms and obesity risk among Egyptian children and adolescents. Genes Dis 2017; 4 (03) 170-175
- 44 Krishnan M, Thompson JMD, Mitchell EA. et al. Analysis of association of gene variants with obesity traits in New Zealand European children at 6 years of age. Mol Biosyst 2017; 13 (08) 1524-1533
- 45 García-Solís P, Reyes-Bastidas M, Flores K. et al. Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) SNP are positively associated with obesity and blood pressure in Mexican school-aged children. Br J Nutr 2016; 1-7
- 46 Villalobos-Comparán M, Teresa Flores-Dorantes M, Teresa Villarreal-Molina M. et al. The FTO gene is associated with adulthood obesity in the Mexican population. Obesity (Silver Spring) 2008; 16 (10) 2296-2301