Figure 3.An example of gene-environment interaction in the pathogenesis of diabetes. The incidence of obesity and type 2 DM has increased dramatically in the native Oji-Cree population in Northern Canada. A glycine to serine (G/S) mutation in the transcription factor HNF-1Î±, which regulates insulin gene expression, was found in a proportion of this population. The effect of this diabetes susceptibility gene is to accelerate the onset of diabetes caused by lifestyle factors. In A, the age of onset of DM is plotted for the entire diabetic population, while in B, the population is divided into those with wild-type (G/G) HNF-1Î±, heterozygotes (G/S) HNF-1Î±, and homozygous mutant (S/S) HNF-1Î±. Each copy of the mutant HNF-1Î± accelerates the onset of diabetes by ~ 7 years. (Reproduced with permission from ref 56).