Association of the rs17782313, rs17773430 and rs34114122 Polymorphisms of/near MC4R Gene with Obesity-Related Biomarkers in a Spanish Pediatric Cohort.

Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.

Short Sleep Duration Is Related to Emerging Cardiovascular Risk Factors in Obese Children.

OBJECTIVE: The aim of the present study was to evaluate the influence of sleep duration on cardiovascular risk factors in obese children. METHODS: Cross-sectional analysis of 90 obese children ages 7 to 16 years. Anthropometric and clinical evaluation with specification of dietary and lifestyle habits was carried out during an office visit. Sleep duration was evaluated by the BEARS (B = bedtime issues, E = excessive daytime sleepiness, A = night awakening, R = regularity and duration of sleep, S = snoring) questionnaire on children's sleep characteristics. Sleep time adequacy by age was assessed according to the criteria of the National Sleep Foundation. Biochemical blood variables indicative of metabolic risk (glucose, lipid profile, and insulin) were obtained. Emergent new factors of metabolic risk, including high-sensitive C-reactive protein, γ-glutamyltranspeptidase, homocysteine, retinol-binding protein 4 (RBP4), thyroid-stimulating hormone (TSH), inflammatory markers, and the adipokines leptin, adiponectin, and ghrelin were also evaluated. The relations between the duration of sleep and these variables were analyzed by general lineal model analysis. Significant variables were introduced in logistic regression analysis to determine the odds ratio (OR) and 95% confidence interval (CI) of cardiometabolic factors with respect to sleep. RESULTS: Children who slept for short duration were significantly more at risk of severe central obesity. In the regression model, the mean arterial pressure (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.17, P = 0.008), homocysteine (OR 1.41, 95% CI 1.08-1.84, P = 0.013), RBP4 (OR 1.78, 95% CI 1.15-2.78, P = 0.010), and TSH (OR 2.01, 95% CI 1.21-3.34, P = 0.007) remain as significant independent predictors related to short sleep duration. We did not find any association between sleep duration and inflammatory markers or adipokines. CONCLUSIONS: Short sleep duration increases the severity of obesity and is related to cardiovascular risk factors in children.

Plasma resistin levels are associated with homocysteine, endothelial activation, and nitrosative stress in obese youths.

OBJECTIVE: To evaluate whether serum resistin levels are related to cardiovascular risk in obese children. DESIGN AND METHODS: Cross-sectional study of 110 children (40 normal weight and 70 severely obese). Clinical and biochemical parameters, including lipid profile, fasting glucose and insulin, and homocysteine, were determined. The levels of adipokines (adiponectin, leptin, and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP)), endothelial activation (serum concentrations of soluble intercellular and vascular cellular adhesion molecule-1 (sICAM-1, sVCAM-1)), and oxidative/nitrosative stress (malondialdehyde and urinary nitrate/nitrite) were measured. RESULTS: A partial correlation adjusted by gender, Tanner stage, and body mass index in obese children showed that resistin was significantly related to central obesity (p<0.002), insulin resistance (p<0.005), and homocysteine (p<0.001). No association was found with other metabolic risk factors or hs-CRP levels. Malondialdehyde (p<0.043) and sVCAM-1 (p<0.002) were positively correlated whereas urinary nitrate/nitrite was negatively correlated (p<0.007). In multiple regression analysis homocysteine, sVCAM-1, and urinary nitrate/nitrite remained independent determinants of resistin levels (R(2) adjusted=0.347, p=0.000). CONCLUSIONS: Resistin could be considered as a promising marker for future cardiovascular disease in obese children.