Influence of genetic and epigenetic modifications on obesity and weight loss in Spanish children and adolescents

Abstract

This Doctoral Thesis reports the role of genetic and epigenetic variations on obesity risk, and weight loss response in three different populations of Spanish children and adolescents between 6 and 18 years old. The first manuscript examines the association of the -174 G/C SNP of the IL-6 gene and adiposity and inflammatory markers. For this purpose, 504 Spanish adolescents from the AVENA study were genotyped for the SNP, body measurements were taken and blood samples were collected. The association between body fat mass and some plasma markers was influenced by the presence of this polymorphism. Adolescents carrying the C allele showed higher values of lipoprotein(a) , C-reactive protein and triglycerides as their body fat mass increases. In the second study, the effect of the rs9939609 of the FTO on obesity risk was studied. The trial involved 354 children and adolescents (GENOI study) following a case-control study. In this study, we confirmed the association between the FTO SNP and obesity risk. Interestingly, an interaction between SFA consumption on the effect and the polymorphism on obesity risk was evidenced. The third research article evaluates the contribution of 9 SNPs on anthropometric and biochemical parameters before and after a weight loss intervention programme in 168 adolescents participating in the EVASYON programme. A genetic predisposition score (GPS) calculated from these polymorphisms revealed a significant effect size on body composition both at baseline and after 10 weeks of treatment. Adolescents with a lower GPS seemed to have greater benefit of weight loss after the intervention. Finally, the fourth publication explored baseline changes in DNA methylation that could be associated with a better weight loss response after an intervention in obese/overweight adolescents. A methylation score calculated from differentially methylated genes was associated with changes in anthropometric parameters after treatment. In addition, after a methylation array, five regions showed differential methylation levels between high and low responders to the intervention. In summary, data from the current Doctoral Thesis contribute to provide evidence of the influence that some genetic variants and epigenetic alterations could have on obesity and the weight loss response.