Obesity Associated POMC Gene Polymorphism: Relation To Metabolic Profile And Eating Habits In Obese Egyptian Children

Abstract

The burden of non-communicable diseases has increased in most of the world over the past 10 years especially obesity reaching an alarming level in both adults and children (Ma et al., 2014a). This increasing secular trend in obesity is also noticed in the Arab world with apparent variations between countries of different income level. The genetic influences play an important role in susceptibility of obesity among individuals exposed to the same obesogenic environment, implicating a gene-environment interaction. The central proopiomelanocortin (POMC) neurons form a potent anorexigenic networkandseveral studies reveal that mutation of the POMC gene has been associated with early-onset obesity. To examine the contribution of the POMC gene in the susceptibility of obesity, we studied a previously described polymorphism consisting of a 9-bp insertional polymorphism, AGC AGC GGC, between nucleotides 6979 and 6998 of the POMC gene. The aim of our study was to assess the POMC gene 9bp insertional polymorphism in obese children and adolescents as well as assessing the relation of this polymorphism to BMI, adiposity-related co-morbidities and binge eating disorder. This case-control study included fifty children and adolescents with simple obesity (27 males and 23 females) recruited from the Pediatric Obesity Clinic, Children’s hospital, Ain Shams University during the period from January 2014 till the end of August 2014.Their mean age was 8.99 ± 3.21 years (Range: 3-16 years). They were compared to fifty age- and sex- and pubertal stage- matched healthy non obese children and adolescents as a control group (27 males and 23 females), their mean age was 8.63 ± 3.42 (Range: 3-15.61 years). All were subjected to full medical history, thorough physical examination laying stress on blood pressure and auxological measurements, psychometric study using the DSM-5 to detect binge eating disorder, laboratory investigations for fasting lipid profile, fasting insulin, fasting glucose, ALT and POMC gene 9bp polymorphism. Abdominal ultrasound was also done. Cases had significantly higher values as regards weight SDS, height SDS, BMI SDS, waist circumference SDS, hip circumference SDS,waist/hip ratio SDS and blood pressure percentiles than the controls.Cases also showed higher levels of ALT, fasting glucose, fasting insulin, HOMA-IR and fasting lipid profile. In addition, we found that the presence of non alcoholic fatty liver disease and the Binge Eating Disorder were significantly higher in cases than in controls. There was no statistically significant difference between cases and controls regarding POMC gene 9bp insertional polymorphism with 68% of cases and 70% of the controls having the polymorphism in the heterozygous form; however, this polymorphism was significantly associated with higher fasting insulin levels in obese cases compared to controls, indicating that the effect of POMC polymorphism on insulin levels may be noticed only in obese children. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects, indicating a possible gene-environment interaction and suggesting that this POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity.