Association between polymorphisms in leptin, leptin receptor, and β-adrenergic receptor genes and bone mineral density in postmenopausal Korean women

Abstract

The purpose of this study was to investigate the association between single nucleotide polymorphisms in leptin (LEP), leptin receptor (LEPR), and β-adrenergic receptor (ADRB) genes and bone mineral density (BMD) in postmenopausal Korean women. LEP c.280G>A, LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C, LEPR c.2096C>T, ADRB2 c.46A>G, ADRB2 c.79C>G, ADRB2 c.718T>C, ADRB2 c.741G>T, ADRB2 c.769G>A, and ADRB3 c.190T>C polymorphisms were analyzed in 592 postmenopausal Korean women. Serum levels of leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, bone alkaline phosphatase, and carboxy-terminal telopeptide of type I collagen were measured, and BMDs at the lumbar spine and femoral neck were also examined. Among the polymorphisms measured, only the LEPR c.1968G>C polymorphism was found to be associated with BMD at the femoral neck, and higher BMD was observed with increasing number of G alleles (P = 0.04). Osteoporosis at the femoral neck was 3.27 and 3.89 times more frequently observed in the AG and GG genotypes than in the AA genotype in the ADRB2 c.46A>G polymorphism (P = 0.024 and P = 0.015, respectively). However, no significant differences in serum levels of leptin, soluble leptin receptor, free leptin index, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone turnover markers were detected among single and haplotype genotypes. These results suggest that the LEPR c.1968G>C polymorphism may be one of the genetic factors affecting femoral neck BMD in postmenopausal Korean women and that an analysis of the ADRB2 c.46A>G polymorphism may be useful in identifying women at risk for osteoporosis at the femoral neck.