[Genetic determinants of obesity. Current issues]

Abstract

A small number of confirmed major genes for human obesity has been identified by molecular genetic studies; mutations of these have a strong influence on the development of excessive body weight. However, the underlying mutations are rare and do not explain the current obesity epidemic. The genetic predisposition to common obesity most likely has a polygenic basis, and each single gene variant has only a small influence on body weight. The introduction of genome-wide association scans (GWAS) offers new opportunities for the study of complex diseases. The receptor variant with the amino acid isoleucin (wildtype: valine) at position 103 of the melanocortin-4 receptor (MC4R) represents the first confirmed polygenic variant with an influence on body mass index; additional polymorphisms located 188 kb at the 3' end of the MC4R have also been shown to have an effect on body weight. Variants in the first intron of the "fat mass and obesity associated" gene (FTO) confer the most pronounced polygenic effect on obesity (+0.4 kg/m(2) per allele); these variants were originally detected in 2007 in GWAS pertaining to type 2 diabetes mellitus. Recently, additional SNPs with a polygenic effect on obesity have been identified in three large GWAS. By December 2009, 17 solidly confirmed polygenes for body weight regulation have been reported.