The Influence Of Polymorphisms In The Tnf Alpha- And Leptinreceptor Gene On Therapy Outcome In The Treatment Of Obese Children

Abstract

The development of obesity is based on genetic and environmental factors. The impact of genetic predisposition for the outcome of obesity treatment programs, especially in childhood, is still unknown. The genes coding for tumor necrosis factor alpha (TNFalpha) and Leptinreceptor (LEPR), are two potential candidate genes for the variation in these phenotypes. PURPOSE: The aim of our study was to investigate the association between the genetic polymorphisms TNF alpha G308A and LEPR Gln223Arg with therapy induced changes in body composition, physical fitness and LDL cholesterol values in obese children. METHODS: 376 obese children (221 girls, 155 boys, age 8-18years, BMI over 97th percentile) were investigated before and after a 4-6 week in-patient treatment program, including calory reduced diet, a regular physical training program and behaviour therapy lessons. Measured phenotypes included height, weight, waist circumference, blood pressure, cholesterol, triglycerides, glucose, TSH levels and a standard bicycle ergometry. The two SNP's: TNFalpha G308A and LEPR Gln223Arg were analyzed using standard PCR-RFLP methods. RESULTS: Both polymorphisms were in Hardy-Weinberg equilibrium. Changes in physical performance were associated with the genotype distribution in the TNFalpha gene (p<0,05). We did not found further associations between pre-intervention phenotypes or changes in phenotypes under the therapeutic intervention for the two investigated polymorphisms. CONCLUSIONS: In summary, we found first evidence that a polymorphism in the gene encoding for TNFalpha may influence in parts the outcome of an intervention program in the treatment of obese children.