Genetic determinants of plasma triglyceride levels in (OLETF x BN) x OLETFbackcross rats

Altered lipid metabolism is closely associated with diabetes in humans, alt hough predisposing genetic factors that affect hyperlipidemia have not yet been clarified. Our previously established OLETF strain is an obese rat mod el of type II diabetes, exhibiting hypertriglycemia as well as hyperinsulin emia, hyperglycemia, insulin resistance, and abundant abdominal fat. To ide ntify genetic factors responsible for dyslipidemic phenotypes in OLETF rats , we performed a whole-genome scan using 293 male (OLETF x BN) x OLETF back cross rats. Our analysis identified two significant quantitative trait loci (QTLs), on rat chromosomes 1 and 8, that are related to fasting triglyceri de levels. The chromosome 1 QTL colocalized with Dmo1 (diabetes mellitus, O LETF type 1), a locus previously shown to associate strongly with both fat levels and body weight. The other significant QTL localizes to the chromoso me 8 marker D8Mit2, in a region where several apo-lipoprotein genes are clu stered. (C) 1999 Academic Press.