Association between Wnt signaling pathway gene polymorphisms and bone response to hormone therapy in postmenopausal Korean women

Abstract

The aim of this study was to explore the association between Wnt signaling pathway gene polymorphisms and response to hormone therapy (HT) as related to bone mineral density (BMD) in postmenopausal Korean women. The BMD and serum levels of osteoprotegerin, the soluble receptor activator of the nuclear factor κB ligand, and bone turnover markers were measured in 308 postmenopausal women receiving sequential estrogen + progestogen therapy. Results were analyzed according to the low-density lipoprotein receptor--related protein (LRP5) 5 c.266A > G, c.3893C > T, frizzled receptor 6 gene c.1033A > C, axin II c.148C > T, adenomatous polyposis coli c.5645T > A, and T-cell factor 1 c.766G > A polymorphisms. The rates of 1-year changes in BMD and changes at 6 months in osteoprotegerin, soluble receptor activator of the nuclear factor κB ligand, and bone turnover markers after HT did not differ significantly between all single and haplotype genotypes of the genes studied. When a nonresponder was defined as a woman who had lost more than 3% of BMD per year after HT, women with T allele of the LRP5 c.3893C > T polymorphism showed a significantly higher risk of nonresponse at both the lumbar spine and femoral neck than did women with C allele. The risk of nonresponse at the lumbar spine was significantly higher in women with G allele of the LRP5 c.266A > G polymorphism than that in women with A allele, and the c.266G/c.3893T (GT) haplotype allele showed a similar trend. The LRP5 c.266A > G and c.3893C > T polymorphisms may be associated with risk of nonresponse to HT in postmenopausal Korean women.