Association of amino acid variation (Trp64Arg) in the beta3-adrenergic receptor gene with bone mineral density


Mitsuru Emi, MD, PhD, Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1–396 Kosugi-cho, Nakahara-ku, Kawasaki 211–8533, Japan. Email:


Background:  Recent studies have revealed that a mis-sense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) of the beta3-adrenergic receptor (β3-AR) gene was associated with insulin resistance in non-diabetic subjects and to earlier onset of non-insulin dependent diabetes mellitus. To analyze a possible involvement of β3-AR in bone metabolism, we investigated the association between bone mineral density (BMD) and the Trp64Arg polymorphism.

Methods:  A large cohort of Japanese postmenopausal women comprised the study population. The genotypic frequencies in this cohort were Trp/Trp, 61.8%; Trp/Arg, 33.2%; and Arg/Arg, 5.0%.

Results:  When the subjects were separated into two groups, one bearing at least one Trp allele at codon 64 (Trp/Trp and Trp/Arg) and the other with none (Arg/Arg), the former subjects had significantly higher Z scores for total-body BMD (mean ± SD, 0.432 ± 0.93 versus −0.135 ± 0.93; P = 0.033).

Conclusions:  These data suggested an association between this single-nucleotide polymorphism (SNP) in the β3-AR gene and BMD, and therefore a possible involvement of the Arg allele (or the absence of Trp64) in postmenopausal osteoporosis among Japanese women.