Postprandial plasma lipid levels are influenced by the interaction of functional polymorphisms in the microsome triglyceride transfer protein and beta3 adrenergic receptor genes.
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.
Keywords: Carrier Proteins - metabolism, Animals, Adult, Genotype, Glucose - metabolism, Humans, Middle Aged, Polymorphism, Genetic, Postprandial Period, Rats, Receptors, Adrenergic, beta-3 - metabolism, Triglycerides - blood