In This Issue of Diabetes

摘要

A variant in the gene that encodes IGF2 is likely associated with a ～20% reduced risk for type 2 diabetes. Mercader et al. (p. 2903) say their findings suggest that reducing the expression of isoform 2 of IGF2 in certain tissues is potentially a new therapeutic target for type 2 diabetes. The claims come from a study that compared many thousands of genetic variants in ～8,200 individuals with type 2 diabetes and just under 13,000 individuals without the disease. All were of Latino descent. As well as, identifying variants that had previously been linked to type 2 diabetes, the authors detail a novel site in IGF2 that is potentially protective. Reportedly, individuals who were heterozygous carriers of the variant had a 22% reduced risk of type 2 diabetes, whereas homozygous carriers had a 40% reduced risk. Overall, the authors found that 17% of the population in Mexico carries the protective allele. They go on to describe a series of experiments in which they show that the variant prevents splicing between exons 1 and 2 of IGF2 and is specifically associated with an allele-dosage-dependent reduction in the expression of isoform 2 of IGF2. On that basis, they say that targeting the variant pharmacologically could yield positive outcomes in individuals without the protective allele, including those from populations where the variant is not present. Author Jose C. Florez told Diabetes: "Finding a genetic association is only the first step toward elucidating molecular mechanism and direction of effect, both of which we have pursued here to begin translating genetics into therapeutics. Our study also illustrates the advantages of studying diverse populations to undertake genetic discovery and the power of philanthropy and collaboration in driving new understanding."