Paternal transmission of the very common class I INS VNTR alleles predisposes to childhood obesity

To identify some of the genetic factors that contribute to obesity in children of Central European and North African descent, we studied the parental transmission of alleles at the insulin locus to offspring with early-onset obesity. A variable nucleotide tandem repeat (VNTR) polymorphism upstream of the insulin gene (INS) is associated with variations in the expression of INS and the nearby gene encoding insulin-like growth factor 2 (IGF2). We found an excess of paternal transmission of class I VNTR alleles to obese children: children who inherited a class I allele from their father (but not those inheriting it from their mother) had a relative risk of early-onset obesity of 1.8. Due to the frequency of class I alleles in this population, this risk concerns 65-70% of all infants. These results suggest that increased in utero expression of paternal INS or IGF2 due to the class I INS VNTR allele may predispose offspring to postnatal fat deposition.