Dissociation of epistatic effects involved in fasting and postprandial hyperglycemia

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. Our previous study has identified four epistatic interactions between Nidde1 (chromosome 7) and 2/of (chromosome 14), Nidde1 and 3/of (chromosome 15), Nidde2 and 4/of (chromosome 15), and Nidde2 and 5/of (chromosome 17), which exerted effects on NIDDM, by performing least squares analysis of variance of all pairs of informative markers in 160 F₂ progenies bred from the OLETF rat. In the present study, we found that the four interactions affect postprandial glucose metabolism, but not glucose levels during fasting states. In addition, we identified novel interactions between Nidde6 (chromosome 1) and 7/of (chromosome 13), and Nidde8 (chromosome 5) and 9/of (chromosome 19), which is involved in fasting glucose levels but not postprandial glucose levels. These findings demonstrate that distinction between genetic bases of fasting hyperglycemia and postprandial hyperglycemia is made by not only single main effect but also epistatic interaction effect of NIDDM loci.