Genetic Determinants of Plasma Triglyceride Levels in (OLETF × BN) × OLETF Backcross Rats |
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| Authors: | Shiro Okuno Takeshi K. Watanabe Toshihide Ono Yuki Yamasaki Yoshihiro Goto Hideo Miyao Toshihiro Asai Naohide Kanemoto Keiko Oga Ayako Mizoguchi-Miyakita Toshihisa Takagi Ei-ichi Takahashi Yusuke Nakamura Akira Tanigami |
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| Affiliation: | a Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd. 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan;b Laboratory of Genome Database, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo, 108-8639, Japan;c Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo, 108-8639, Japan |
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| Abstract: | Altered lipid metabolism is closely associated with diabetes in humans, although predisposing genetic factors that affect hyperlipidemia have not yet been clarified. Our previously established OLETF strain is an obese rat model of type II diabetes, exhibiting hypertriglycemia as well as hyperinsulinemia, hyperglycemia, insulin resistance, and abundant abdominal fat. To identify genetic factors responsible for dyslipidemic phenotypes in OLETF rats, we performed a whole-genome scan using 293 male (OLETF × BN) × OLETF backcross rats. Our analysis identified two significant quantitative trait loci (QTLs), on rat chromosomes 1 and 8, that are related to fasting triglyceride levels. The chromosome 1 QTL colocalized with Dmo1 (diabetes mellitus, OLETF type 1), a locus previously shown to associate strongly with both fat levels and body weight. The other significant QTL localizes to the chromosome 8 marker D8Mit2, in a region where several apo-lipoprotein genes are clustered. |
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