Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is associated with increased plasma leptin levels in obese Chinese women.

BACKGROUND

beta 3-Adrenergic receptors are predominantly expressed in the fat cells of visceral adipose tissue in humans. They mediate catecholamine-induced lipolysis and thermogenesis of adipose tissue, which are important for the regulation of energy expenditure and, therefore, body weight. Recently, a Trp64Arg polymorphism of the beta 3-adrenergic receptor gene was reported to be associated with obesity and obesity-related metabolic complications in some ethnic populations. Leptin, a protein secreted by adipocytes, is proposed as a signal linkage between the central nervous system and peripheral fat storage. It has been shown in rodents that leptin may activate the sympathetic nervous system and, thus, beta 3-adrenergic receptors in adipose tissue. However, little is known about the relationship between the Trp64Arg polymorphism and plasma leptin in humans.

METHODS

To determine the effects of the beta 3-adrenergic receptor gene Trp64Arg mutation on anthropometric measures, metabolic parameters and plasma leptin levels, 188 premenopausal Chinese women (mean age +/- standard deviation, 32 +/- 10 years) with body mass index (BMI) between 16.1 and 59.8 kg/m2 were investigated. Trp64Arg polymorphism was determined by DNA analysis, body fat mass by bioelectric impedance analysis and plasma leptin by radioimmunoassay.

RESULTS

Trp64Arg allele frequency was 15% in this population and there was no homozygous Arg64Arg mutant. When the subjects were divided into three groups based on BMI values (BMI < 22.2, n = 60; 22.2 < or = BMI < or = 29.5, n = 63; BMI > 29.5 kg/m2, n = 65), there was no difference in Trp64Arg allele frequency (16% vs 11% vs 18%, p = 0.149). Across the three groups, plasma leptin correlated positively with BMI (r = 0.843, p < 0.0001) and total fat mass (r = 0.824, p < 0.0001). Within each BMI tertile, the waist to hip ratio, fat mass, plasma lipids, glucose and insulin were relatively similar between Trp64Trp homozygotes and Trp64Arg heterozygotes. However, Trp64Arg heterozygotes had higher plasma leptin levels than Trp64Trp homozygotes (35.9 +/- 11.0 vs 30.0 +/- 12.8 ng/ml, p = 0.0023) in those with BMI above 29.5 kg/m2, a difference which remained after adjustment for body fat mass (p = 0.024).

CONCLUSIONS

Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity in Chinese women. Plasma leptin concentrations correlate well with BMI and total fat mass. For obese Chinese women, the Trp64Arg genotype of the beta 3-adrenergic receptor gene may contribute to an increased plasma leptin level.