Génétique de l’obésité

Abstract

Obesity is a complex disease resulting from the interaction of genetic and environmental factors. Combined progress in quantitative genetics, genomics and bioinformatics have contributed to increase our knowledge of genetic and molecular bases of obesity. It is now well established that overweight and the various forms of obesity are characterized by familial resemblance. Studies have shown that the risk of obesity was 2 to 8 times higher in an individual with positive family history compared to an individual without family history and that this risk tends to be higher for severe cases of obesity. The heritability of obesity depends of the phenotype investigated and tend to be higher for phenotypes associated with fat distribution (40 % to 55 %) than for phenotypes associated with excess body mass or adiposity (5 % to 40 %). Weight gain and changes in adiposity with age are also influenced by genetic factors. The existence of monogenic forms of obesity provides an indication that obesity could result from mutations in single genes, but only 78 cases due to mutation in 7 different genes have been reported so far. The most common forms of obesity are undoubtedly caused by variations in a large number of genes. DNA sequence variations in 56 different genes have been reported to be asociated with various obesity phenotypes so far, but only 10 of these genes have been associated with obesity in at least 5 different studies. In summary, we can conclude from the evidence accumulated so far that genetic factors play a role in the etiology of obesity and that except for rare cases of severe obesity, the genes involved are genes interacting with environmental factors related to energy intake and energy expenditure to increase the risk of obesity in susceptible individuals. The identification of these susceptibility genes is the task awaiting the hunters of obesity and related co-morbidity genes in the next decade.