The Relation between Childhood Obesity and MC4R Gene and Near MC4R Polymorphisms

  • Ozgur Erkal
  • Mehmet Ali Ergün
  • Mehmet Boyraz
  • Aysun Bideci
  • Peyami Cinaz


Childhood obesity, especially in the developed countries including all over the world has an increasing prevalence. Regarding the major impact on public health perspective, childhood obesity should be monitored closely. Many researchers reported MC4R gene and near MC4R region polymorphisms to predispose monogenic obesity both in children and adults. In this study we investigated the relation between childhood obesity and Ser58Cys, Val50Met, Ile102Ser, Val103Ile, Asn274Ser,  rs17782313 and rs17700633 polymorphisms in MC4R gene and near MC4R region in the Turkish population.  It is very important to detect single gene disorders that may cause childhood obesity in order to screen children for the predisposition of obesity, as to protect them from environmental factors that may cause weight gain.


-Keller C, Stevens KR. Assesment, etiology, and intervention in obesity in children. Nurse Pract. 1996; 21: 31-36, 38, 41-42.

-Martorell R, Kettle K, Hughes ML, Grummer-Stawn ML. Overweight and obesity in preschool children from developing countries. International Journal of Obesity 2000; 24:959-67.

-Young TK, Dean HJ, Flett B, Wood-Steiman P. Childhood obesity in a population at high risk for type 2 diabetes. J. Pediatr. 2000;136:365-9.

-List JF, Haberner JF. Defective melanocortin 4 receptors in hyperphagia and morbid obesity. N. Engl. J. Med. 2003;348:1160-3.

-Farooqi IS, Keogh JM, Yeo G.S, Lank EJ, Cheetham, T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 2003; 348: 1085–95.

-Gotoda T, Scott J, Aitman TJ. Molecular screening of the human melanocortin-4 receptor gene: Identification of a missense variant showing no association with obesity, plasma Glucose, or insulin Diabetologia 1997; 40:976-979.

-Mergen M, Mergen H, Ozata M, Oner R, Oner C. A novel melanocortin 4 receptor (MC4R) gene mutation associated with morbid obesity. J. Clin. Endocrin. Met. 2001;86: 3448-51.

-Qi L, Kraft P, Hunter DJ, Hu FB. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Human Molecular Genetics 2008;17:3502-8.

-Dubern B, Clement K, Pelloux V, Froguel P, Girardet JP, Guy-grand B. Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. J. Ped. 2001;139:204-9.

-Vaisse C, Clement K, Durand E, Hercberg S, Guybrand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity J. Clin. Invest. 2000; 106 :253-62.

-Yurtcu E, Yilmaz A, Ozkurt Z, Kolukisa E, Yilmaz M, Keles H, et al. Melanocortin-4 receptor gene polymorphisms in obese patients. Biochem. Genet. 2009;47:295-300.

-Farooqi IS, Yeo GSH, Keogh JM, Aminian S, Jebb SA, Butler G. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency J. Clin. Invest. 2000;106:271-9.

- Hinney A, Schmidt A, Nottebom K, Heibült O, Becker I, Ziegler A et al. Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J. Clin. Endocrinol. Metab. 1999; 84:1483–6.

-Reinehr T, Hebebrand J, Friedel S, Toschke MA, Brumm H, Biebermann H. Lifestyle Intervention in Obese Children With Variations in the Melanocortin 4 Receptor Gene. Obesity 2009:17;282-9.

-Kring SI, Holst C, Toubro S, Astrup A, Hansen T, Pedersen O. Common variants near MC4R in relation to body fat, body fat distribution, metabolic traits and energy expenditure. International Journal of Obesity 2010;34:182-9.

-Loos RJF, Lindgren CML, Li S, Wheeler F, Zhao JH, Prokopenko I. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genetics 2008; 40:768-75.

Literature Review With Cases