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Takahiro Ueno, Yumiko Takahashi, Taro Matsumoto, Akiko Tsunemi, Hideyuki Watanabe, Kazunobu Tahira, Noboru Fukuda, Masayoshi Soma, Koichi Matsumoto
Med Sci Monit 2007; 13(5): BR112-118
Background: The effects of polymorphisms in the genes encoding microsome triglycerides transfer protein (MTP) and beta3-adrenergic receptor (beta3-AR) on lipid and glucose metabolism were investigated. Material/Methods: Clinical phenotypes related to lipid and glucose metabolism were evaluated during dietary loading (17 g of fat, 750 Cal) and glucose loading (75 g glucose). MTP and beta3-AR genotypes were determined by restriction fragment length polymorphism. Results: Subjects with the Arg64 beta3-AR gene (Arg+) polymorphism showed significantly higher fasting (FTG) and postprandial (PTG) triglyceride levels, fasting plasma glucose (FPG), fasting plasma immuno-reactive insulin (FIRI) and HOMA-R in comparison with Trp64 homozygotes. Subjects with the T allele (T +) of MTP -164T/G polymorphism (with T allele) showed significantly lower levels of FPG, FIRI, HOMA-R and PTG than did subjects without the T allele (T-). To evaluate the interaction of the polymorphisms, we divided our subjects into four groups. T-/Arg-, T-/Arg+, T+/Arg- and T+/Arg+. In these four groups, only T-/Arg+ showed significantly higher PTG levels. Plasma glucose levels were significantly higher at 60 and 120 min after oral glucose loading in in the T-/Arg+ subjects. Conclusions: In this study, we identified an example of genotypic interactions that influence the clinical phenotype in multi-factorial diseases.