Postprandial plasma lipid levels are influenced by the interaction of functional polymorphisms in the microsome triglyceride transfer protein and beta3 adrenergic receptor genes.
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.


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.
Ueno
Takahiro
T
Department of Medicine, Division of Nephrology and Endocrinology, Nihon University School of Medicine, Tokyo, Japan. tueno@med.nihon-u.ac.jp
Takahashi
Yumiko
Y
Matsumoto
Taro
T
Tsunemi
Akiko
A
Watanabe
Hideyuki
H
Tahira
Kazunobu
K
Fukuda
Noboru
N
Soma
Masayoshi
M
Matsumoto
Koichi
K
D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D051381:Rats; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood*
D002352:Carrier Proteins; D022702:Receptors, Adrenergic, beta-3; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D005947:Glucose