An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity


  • P. Kuehnen
  • M. Mischke
  • S. Wiegand
  • C. Sers
  • B. Horsthemke
  • S. Lau
  • T. Keil
  • Y.A. Lee
  • A. Grueters
  • H. Krude


  • PLoS Genetics


  • PLoS Genet 8 (3): e1002543


  • The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron2-exon3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon3 methylation variant seems to result from an Alu element-triggered default state of methylation boundary definition. Exon3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity.