The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with increased small dense low-density lipoprotein in a rural Japanese population: the Mima study.
The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.
Tsuzaki
Kokoro
K
Department of Preventive Medicine, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
Kotani
Kazuhiko
K
Fujiwara
Shinji
S
Sano
Yoshiko
Y
Matsuoka
Yukiyo
Y
Domichi
Masayuki
M
Hamada
Taku
T
Shimatsu
Akira
A
Sakane
Naoki
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D007564:Japan; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics* / Q000378:metabolism; D012424:Rural Population
D001786:Blood Glucose; D007328:Insulin; D008077:Lipoproteins, LDL; D022702:Receptors, Adrenergic, beta-3; D004247:DNA