Polymorphism in the 5'-flanking region of the human insulin gene and the incidence of diabetes.

DNA length polymorphism in the 5'-flanking region of the human insulin gene has been reported by Bell et al. (1981), Rotwein et al. (1981), and Owerbach and Nerup (1982). Bgl I digestions of human DNA that have been hybridized to an insulin probe using the Southern technique shows that there are two distinct groups of 5'-flanking lengths: one being shorter than 3.6 kilobases (kb) and the other being longer than 4.3 kb. The insulin genes with the former length are denoted as A1, and those with the latter as A2. Using these data and demographic data of diabetes, it is estimated that, when the fitness of A1 A2 individual was taken as unity, the amounts of fitness reduction for A1 A1 was 6.5 X 10(-6) and that for A2 A2 was -5.6 X 10(-6). Because of these small magnitudes of selection, the changes in population incidences of insulin-dependent diabetes and noninsulin-dependent diabetes are not affected much by the polymorphism in the 5'-flanking region of the insulin gene.