Association between anthropometric measures of obesity, metabolic disturbances and polymorphism G-308A of the tumor necrosis factor-alpha gene in children

INTRODUCTION: TNF-α is one of the most important factors in the development and course of inflammation. It is suggested that polymorphism located in the 5'regulatory region of the TNF-α gene at position 308 (guanine [G]→ adenine[A]) may increase the expression of this cytokine in fat tissue and influence the fat mass and insulin resistance. OBJECTIVE: To investigate whether the G-308A polymorphism of the TNF-α gene may influence obesity, insulin resistance, fasting plasma lipids, serum leptin levels, and the incidence of metabolic syndrome. MATERIALS AND METHODS: The obese group included 124 children with simple obesity (72 girls and 52 boys) aged 10-18 (mean age 15 years) with SDS of BMI ≥ 2.0. A control group consisted of 56 healthy non-obese children (36 girls and 20 boys) aged 11-18 (mean age 14 years) with SDS of BMI < 1.0. Polymorphism identification was performed in total genomic DNA, using PCR-RFLP method. RESULTS: Carriers of A (AG+AA) allele among the obese children were significantly more frequent than in the control group (OR = 2.29, 95% CI 1.2-4.4, χ(2)= 6.24, P < 0.05). Carriers of A alleles showed a higher concentrations of fasting glucose (81.3 ± 10.5 vs. 77.4 ± 10.3 mg/dl; P < 0.05), but lower values of fasting insulin (15.1 ± 7.3 vs. 19.0 ± 9.5 μIU/ml; P < 0.05), lower values of HOMA index (3.0 ± 1.5 vs. 3.7 ± 2.0; P < 0.05). In the group of boys, carriers of A alleles showed a tendency for lower concentrations of HDL (43.8 ± 12.6 vs. 48.3 ± 11.8 mg/dl; P < 0.05). Blood pressure and leptin level did not differ between the obese children with gene polymorphism and those of wild homozygous. The incidence of the full metabolic syndrome (MetS) in the children, according to the IDF definition, was 33%. The presence of the MetS in children with wild homozygous GG and carriers of A allele of TNF-α polymorphism gene did not show statistical differences (OR = 1.38; 95% CI 0.6-3.1, χ(2)= 0.58). CONCLUSIONS: 1/Polymorphism G-308A of the TNF-α gene is more common in children with obesity; and 2/Polymorphism G-308A of the TNF-α gene does not seem to be associated with the grade of obesity, insulin resistance, lipid profile, leptin levels, and the incidence of metabolic syndrome in obese children.