β₃ Adrenergic Receptor Polymorphism and Obesity‐Related Phenotypes in Hypertensive Patients

Abstract

Adrenergic receptor polymorphism and obesityrelated phenotypes in hypertensive patients. Obes Res. 2004;12:125-130. Objectives: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The ␤ 3 adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. Research Methods and Procedures: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men, 359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. Results: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p Ͻ 0.001) and had a BMI that was 3.7 kg/m 2 greater (p ϭ 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. Discussion: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.

Comparison of Body Fat Distribution and Blood Lipid Profiles according to Trp64Arg Polymorphism for the .BETA.3-Adrenergic Receptor Gene in Korean Middle-Aged Women

“…Hao et al (23) suggested no significant association of Trp64Arg polymorphism of the ␤3-adrenergic receptor gene with serum levels of triglyceride, cholesterol, or glucose in Chinese hypertensive women.…”

Pharmacogenetics of Ophthalmic Topical β-Blockers

“…This SNP, T727C, encodes an amino acid substitution (Trp64Arg) in the first transmembrane-spanning region of ADRB3, near its N-terminus. In a series of 695 adult Chinese subjects, this ADRB3 SNP was associated with weight and BMI in men but not in women [52]. A similar effect was observed in 295 adult Japanese men, but only when the data were adjusted for energy intake [51].…”

“…In a study of 643 American women (representing both European and African heritage), no association was observed between this ADRB3 SNP and any obesity phenotypes (i.e., BMI, waist circumference and waist:hip ratio [50]). The reason for gender discrepancy remains unclear and requires further characterization, since emerging data indicate that gender may impact phenotype in the context of glaucoma treatment [52].…”

“…In a study of 643 American women (representing both European and African heritage), no association was observed between this ADRB3 SNP and any obesity phenotypes (i.e., BMI, waist circumference and waist:hip ratio [50]). The reason for gender discrepancy remains unclear and requires further characterization, since emerging data indicate that gender may impact phenotype in the context of glaucoma treatment [52].The role of adrenergic receptor polymorphisms in variability of IOP response to β-blockers has recently been investigated. In healthy subjects, the Arg389Gly polymorphism in ADRB1 has been associated with a higher baseline IOP and a greater reduction in IOP following topical betaxolol therapy [53].…”

Single nucleotide variants in the β2-adrenergic and β3-adrenergic receptor genes explained 18.3% of adolescent obesity variation

“…Associations of SNPs at codons 16 and 27 of the ADRB2 gene with obesity have been reported (Ukkola et al 2000), yet the significance of ADRB2-1053G/C in our study was novel. The significance of a common ADRB3 variant replacing tryptophan with arginine (Trp64Arg) on BMI has been shown in both adult (Hao et al 2004) and children (Endo et al 2000;Arashiro et al 2003) populations. ADRB3-Trp64Arg also influenced percentage of body fat (P < 0.01) and plasma leptin level (P < 0.05).…”