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.

Is obesity associated with oxidative stress in children?

OBJECTIVE: We evaluated the presence of oxidative stress in obese children without co-morbidities. METHODS: The study population included 68 children (30 girls, 38 boys), between 6 and 14 years of age. The levels of markers of oxidative damage (malondialdehyde [MDA], and plasma carbonyl groups [CG]) and measures of antioxidant defense, such as the enzyme glutathione peroxidase (GPx) and low molecular scavengers (erythrocyte-reduced glutathione [GSH], alpha-tocopherol and beta-carotene) were determined. Children were categorized in groups by the standard deviation score of body mass index (SDS-BMI). Twenty children were non-obese (SDS-BMI< or =1.33), and the 48 obese children (SDS-BMI> or =2) were further divided into two groups: SDS-BMI> or =3 (22 children) and > or =2 SDS-BMI<3 (26 children). RESULTS: The levels of MDA and CG were significantly higher (p<0.05) in children with SDS-BMI> or =3. The GPx activity was increased, while the GSH concentration was lower in obese children compared with non-obese children (p<0.01). There were no differences in serum alpha-tocopherol and beta-carotene levels between groups. MDA was the sole marker of oxidative damage that was positively correlated with SDS-BMI, (r=0.35, p=0.015), and negatively with high-density lipoprotein cholesterol (HDL-C) (r=- 0.32, p=0.027). GPx was inversely related to total cholesterol (r=- 0.34, p=0.019). In multiple regression analysis, we confirmed that SDS-BMI and HDL-C were determinants of MDA. CONCLUSIONS: Severe childhood obesity is associated with oxidative stress. Thus, providing foods with high antioxidant capacity in addition to a hypocaloric diet is crucial for the treatment of obese children.

Oxidant/antioxidant status and hyperfiltration in young patients with type 1 diabetes mellitus.

Diabetic nephropathy (DN), a major cause of morbidity and mortality in diabetes, will develop within a subset of type 1 diabetes mellitus (T1DM) patients, and oxidative stress has been implicated in its pathogenesis. To investigate the relationship between indicators of early DN stages (hyperfiltration estimated by creatinine clearance > or =150 ml/min per 1.73 m(2), microalbuminuria) and oxidative stress, a prospective study was conducted in 29 T1DM patients (age 13.89 +/- 4.61 years) and 18 control subjects (age 13.23 +/- 3.99 years). Blood samples were collected to assay for biomarkers of oxidative stress (malondialdehyde and carbonyl groups) and antioxidants (glutathione peroxidase, reduced glutathione, alpha-tocopherol, and beta-carotene). With respect to control subjects, in T1DM patients, an increase was found in biomarkers of oxidative stress (p < 0.05), mainly due to the group of subjects with hyperfiltration, and a decrease in the ratio alpha-tocopherol/lipids (p < 0.05). In multiple regression analyses, age at disease onset, glycated hemoglobin, microalbuminuria, and oxidative stress biomarkers remained as explicative variables of hyperfiltration (R (2) adjusted = 0.731, p = 0.000). These findings support the importance of the oxidative damage to lipids and proteins, which is linked to hyperfiltration and which could contribute to the development of DN in patients with T1DM.