Annals of Clinical Biochemistry > Volume 45, Number 3 > Pp. 313-315

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Polymorphism of Trp64Arg in β₃-adrenergic receptor gene and serum LDL-cholesterol concentrations in healthy Japanese

Kazuhiko Kotani^1,2, Naoki Sakane², Youichi Kurozawa¹, Akihiko Kaetsu³, Mikizo Okamoto³, Yoneatsu Osaki³ and Takuji Kishimoto³

¹ Division of Health Administration and Promotion, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan; ² Department of Preventive Medicine, Clinical Research Institute for Endocrine and Metabolic Disease, National Hospital Organization Kyoto Medical Center, Kyoto, 612-8555, Japan; ³ Division of Environmental and Preventive Medicine, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan

Corresponding author: Dr Kazuhiko Kotani. Email: kakotani{at}grape.med.tottori-u.ac.jp

Background: Polymorphism of Trp64Arg in the β₃-adrenergic receptor (β₃-AR) gene may play a critical role in lipid and lipoprotein metabolism by mediating lipolysis and thermogenesis. Since the frequency of Arg alleles of the β₃-AR gene is generally low among many populations, studies on the Arg/Arg genotype in relation to lipid and lipoprotein metabolism are required in countries such as Japan which has a relatively high frequency of the Arg allele.

Methods: We genotyped 275 clinically healthy Japanese (male/female, 134/141, mean 45.7 years) without medication for β₃-AR gene polymorphism by polymerase chain reaction–restriction fragment length polymorphism analysis, and investigated the effects of the gene polymorphism on clinical parameters including body mass index (BMI), blood pressure and serum lipid and lipoprotein concentrations.

Results: The genotype frequencies were: Trp/Trp, 68.0%; Try/Arg, 28.0% and Arg/Arg, 4.0%, with an allele frequency of 0.18 for Arg64. When subjects were divided into three groups according to the genotype, a significant increase of serum LDL-cholesterol (LDL-C) concentration in the Arg/Arg group (3.48 ± 1.59 mmol/L) was observed when compared with those of the Trp/Trp and Arg/Trp groups (3.15 ± 0.80, 3.25 ± 0.92 mmol/L, respectively). Genotype differences did not show any significant effect on other parameters. Spearman's rank correlation demonstrated a significant relationship between LDL-C concentrations and the number of Arg alleles, age and BMI. Multiple regression analysis, using LDL-C concentration as a criterion variable and some factors including β₃-AR gene polymorphism as explanatory variables, revealed that the number of Arg alleles was a significant and independent factor for LDL-C concentrations, along with age and BMI.

Conclusions: These findings suggested a role of the β₃-AR gene polymorphism in regulating lipid and lipoprotein metabolism, showing small but significant effects on elevated LDL-C values in subjects with Arg/Arg, but not Trp/Arg and Trp/Trp genotypes.

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