Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation. Polymorphisms in the LRP5 gene have been associated with either osteoporotic phenotypes or normal bone mineral density (BMD) variation.
Objective: To explore the influence of two LRP5 single nucleotide polymorphisms (SNPs) A1330V and V667M on BMD and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and bone metabolic markers in a Greek female population.
Study design: Two hundred and twenty-one peri- and postmenopausal women aged 4063 years were enrolled. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M polymorphisms was performed by real-time polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured.
Results: Both SNPs were significantly associated with low spinal BMD. As regards A1330V SNP, women carrying CT/TT genotypes had lower spinal BMD than women with CC (P<0.0001). Regarding V667M SNP, spinal BMD was lower in women with GA/AA genotypes than in women with GG (P<0.0001). The associations remained significant after adjustment for age, years since menopause (YSM) and body mass index (BMI). The two SNPs were in strong linkage disequilibrium. A significant interaction between A1330V and V667M SNPs on spinal BMD was revealed. No effect was observed on circulating OPG, sRANKL levels and bone metabolic markers even after adjustment for age, YSM and BMI.
Conclusions: These findings demonstrate that A1330V and V667M polymorphisms of LRP5 gene are strongly implicated to osteoporosis susceptibility in peri- and postmenopausal Greek women.
30 Apr - 04 May 2011
European Society of Endocrinology