Perfiles genéticos de riesgo a padecer obesidad mórbida

Zusammenfassung

Being seriously overweight a perfect example of complex polygenic disease, we present the design and implementation of a protocol for detecting cases of morbid obesity (MO) in the population of Extremadura, whose etiology can be attributed mainly to changes and/or genetic profiles risk. The thesis aims to define causality and heritability model OM in each patient/family included. We worked on three lines of research: 1. Severe obesity associated with mental retardation/dysmorphology. 2. Search for mutations in MC4R high susceptibility genes, the main cause of monogenic obesity, and LEPR. 3. Identification of polygenic risk profiles based on the analysis of SNPs located in 11 genes of susceptibility. We selected 500 individuals affected with severe obesity since before age 14 (> 4SD), referred to the consultation Genetics Unit of the Hospital Infanta Cristina. We have demonstrated the heterogeneity of the genetic basis of the OM, the need for comprehensive assessment of each individual phenotype/family, and application of appropriate diagnostic technology in each case. 1. We have achieved a high diagnostic rate in obesity-associated mental retardation. 2. We have identified the first genetic variants of high-risk morbidly obese population non syndromic Extremadura. 3. Defined hereditary risk profiles based on the number of risk alleles for 6 SNPs in genes associated with disease. Description of the genotype/phenotype correlations. Ensure the use of the results to optimize the clinical management of patients/families affected.