The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels.

Bernhard Horsthemke (1) , Tea Berulava (1)

1 Institut für Humangenetik

As shown by genome-wide association studies single nucleotide polymorphisms (SNPs) within intron 1 of the FTO gene are associated with the body mass index (BMI) and type 2 diabetes, although the functional significance of these SNPs has remained unclear. Using primer extension assays, we have determined the ratio of allelic FTO transcript levels in unspliced heterogeneous nuclear RNA (hnRNA) preparations from blood of individuals heterozygous for SNP rs9939609. Allelic expression ratios of the neighbouring RPGRIP1L gene were investigated in individuals who were heterozygous for SNP rs4784319 and heterozygous or homozygous for rs9939609. In each of five individuals, the FTO transcripts containing the A (risk) allele of rs9939609 were more abundant than those with T allele (mean 1.38; 95% confidence interval 1.31 to 1.44). Similar results were obtained in a fibroblast sample. We also observed skewed allelic expression of the RPGRIP1L gene in blood, but skewing was independent of the FTO genotype. Our data suggest that increased expression of FTO is associated with increased body mass.

Mots clés: FTO; SNP; allelic expression

Bernhard Horsthemke, Tea Berulava. The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels.. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.71⟩. ⟨hal-00540037⟩