Study of obesity associated proopiomelanocortin gene polymorphism: relation to metabolic profile and eating habits in a sample of obese Egyptian children and adolescents

Background: Melanocortinergic system represents a known system involved in the central regulation of body weight with the central proopiomelanocortin [POMC] neurons forming a potent anorexigenic network. Polymorphisms in the POMC gene locus are associated with obesity phenotypes

Aim: To assess the contribution of the POMC gene 9-bp insertional polymorphism in the susceptibility to obesity and its relation to body mass index [BMI] and adiposity-related co-morbidities in obese children and adolescents; as well as binge eating behavior

Patients and methods: Fifty obese children and adolescents with simple obesity were screened for Binge Eating Disorder [BED] by The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5], they were compared to 50 age, sex and pubertal stage-matched non obese controls. Anthropometric measurements, blood pressure, abdominal ultrasound for fatty liver, measurement of fasting lipid profile, fasting insulin, fasting blood glucose and assessment of POMC gene 9-bp insertional polymorphism were done

Results: Obese patients had significantly higher anthropometric measurements, blood pressure percentiles, fasting glucose, fasting insulin, homeostasis model assessment for insulin resistance [HOMA-IR] and fasting lipid profiles, and higher frequency of occurrence of non alcoholic fatty liver disease and BED. Allelic frequencies of POMC gene 9 bp insertional polymorphism were comparable in patients and controls [p= 0.956]. Fasting insulin levels were significantly higher in the heterozygous cases having the polymorphism than in wild homozygous cases; whereas no difference was observed among the controls

Conclusion: This polymorphism was associated with higher fasting insulin levels in the obese patients only. These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects indicating a possible gene-environment interaction. POMC variant may be involved in the natural history of polygenic obesity, contributing to the link between type 2 diabetes and obesity

Health related quality of life and psychological problems in Egyptian children with simple obesity in relation to body mass index

Obesity in childhood or adolescence could affect quality of life [QOL] There is little existing information about the health-related quality of life [HRQOL] of obese children and adolescents. To assess HRQOL and psychiatric co-morbidities in obese children and adolescents; and their relationship to body mass index [BMI]. Fifty obese children and adolescents were compared to 50 healthy age-, sex- and pubertal stage-matched non obese children and adolescents serving as controls. They were assessed by child self-report and parent proxy report using a pediatric HRQOL inventory scale, also, Children Anxiety Scale and Children Depression Inventory [CDI] were assessed. Obese children had total HRQOL score: 69.1 +/- 8.4 versus 81.1 +/- 7.8 respectively, p < 0.001 and their parents had total score: 62.9 +/- 9.5 versus 74.9 +/- 7.2 respectively, p < 0.001. Obese children reported lower health-related QOL scores in all domains than controls. BMI standard deviation score [SDS] correlated negatively with total score and all domains in child self report and parent proxy report. Anxiety [mild: 8%, moderate: 38%, severe: 54%] and depression [mild: 18%, moderate: 24%, severe: 58%] were pre-existing or diagnosed in all obese children with significant positive correlations between BMISDS and each of anxiety [r = 0.81, p < 0.01] and CDI scores [r = 0.78, p = 0.01]. BMI [OR: 5.72, 95%CI: 2.57-5.9] and waist circumference [OR:2.27, 95%CI: 1.99-5.31] SDSs were independent risk factors affecting the total QOL score Obese children and adolescents have lower health-related QOL that correlated negatively with BMI, also they are more susceptible to anxiety and depression symptoms than non obese children

Study of thyroid function in children with attention deficit hyperactivity disorder and aggressive behavior

Attention deficit hyperactivity disorder [ADHD] is a well recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of familial predisposition. Symptoms suggestive of the disorder have been reported in patients with generalized resistance to thyroid hormones [GRTH], a disease caused by a mutation in the thyroid receptor beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to thyroid hormone actions. This study was conducted to assess the frequency of thyroid hormone abnormalities in children with ADHD and/or aggressive behavior and to relate these abnormalities to the type of behavioral disorder. Thirty cases with behavioral disorders [ADHD and/or aggression] diagnosed by DSM-IV classification were studied in comparison to 10 age-and sex-matched healthy controls. Clinical examination and psychiatric evaluation including IQ and psychosocial assessment were done to all patients. Measurement of serum free triiodothyronine [fT3], free tetraiodothyronine [fT4] and thyrotropin [TSH] was done to cases and controls. There was a significantly lower IQ [p <0.05] among patients [84.2 +/- 16.4%] when compared to controls [100.9 +/- 5.4%]. Significantly higher mean fT3 and TSH levels [p <0.05] were detected among cases [5.96 +/- 2.9 pg/ml and 6.53 +/- 3.2 ulU/ml respectively] when compared to controls [2.96 +/- 0.82 pg/ml and 2.28 +/- 1.28 ulU/ml respectively] while a non significant difference [p >0.05] in the fT4 level was detected. Twelve out of our 30 studied cases [40%] had thyroid hormone resistance among whom 7 [23.3%] had high fT3 and high TSH levels while 5 [16.7%] had high fT3 and normal TSH. Among the ADHD group, 3/16 [18.8%] had high fT3 and high TSH levels and 1/16 [6.3%] had high fT3 and normal TSH levels. Among those with aggression, 2/8 [25%] had high fT3 and high TSH and a similar percentage had high fT3 and normal TSH. Among those with both ADHD and aggression, 2/6 [33.3%] had high fT3 and high TSH and a similar percentage had high fT3 and normal TSH. In the 3 groups of behavioral disorders, none of the cases had high fT4 levels above the age-matched controls.A significant number of patients meeting the diagnostic criteria for ADHD have associated RTH. Therefore, measurement of TSH and fT3 should be incorporated in the work up of children in families having ADHD and/or aggression. In children with ADHD and concomitant RTH, particularly those who exhibit hyperactivity, liothyronine [L-T3] in supraphysiological doses could be beneficial in reducing hyperactivity and impulsivity and thus decreasing the need for psychostimulants. Further studies are warranted regarding the role of RTH in the pathophysiology of ADHD

Association between polymorphisms within tumor necrosis factor genes and the development of bronchial asthma among Egyptian children

Tumor necrosis factor [TNF] is a proinflammatory cytokine that is eminently important in the pathogenesis of bronchial asthma. Bronchial asthma is a frequent respiratory disease characterized by variable airflow obstruction, inflammation of the airways, and bronchial hyper-responsiveness [BHR]. In an effort to find out the polymorphism[s] in genes whose variant[s] have been implicated in asthma phenotypes, we examined the genetic effects of TNF [TNFA and TNFB] polymorphisms on the Egyptian asthmatic children. In this study, skin prick test [SPT], total IgE level, pulmonary functions including FVC, PEF, FEV[1] and FEF[25-75], and bronchial asthma hyper-responsiveness [BHR], were investigated. Sixty asthmatic subjects, as defined by standard MRC respiratory questionnaire, plus 40 healthy controls were genotyped for two common single-nucleotide polymorphisms [SNP] using enzymatic digestion of polymerase chain reaction [PCR]. Asthma was significantly more common in subjects with TNFA-1031C>T [P= 0.007]. Although the SNP containing TNFB+252A>G polymorphism might seem to be excluded in our sample as a cause of the disease [P= 0.6], it was in a very strong linkage disequilibrium with TNFA-1031C>T [P= 0.000002]. All the TNFA-1031C>T genotypes were in a strong association with the severity of the asthma. Incidentally, the LT alpha Ncol-AA [80%] was the most predominant genotype with the severe form. However, someone might predict the severity of asthma and consequently the phenotype of an asthmatic individual by knowing the polymorphism of either the TNFA-1031C>T or even the LT alpha Ncol. These findings may have implications for future early intervention studies by helping to identify infants at increased risk for childhood asthma