The association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy in postmenopausal Korean women

Objective: The aim of this study was to explore the association between polymorphisms in Wnt antagonist genes and bone response to hormone therapy (HT) in postmenopausal Korean women. Methods: A prospective study was conducted with 303 postmenopausal women receiving sequential estrogen plus progestogen therapy in a university hospital. The dickkopf (Dkk) 1 c.318A>G, Dkk2 c.437G>A, Dkk3 c.1003A>G, secreted frizzled-related protein (sFRP) 1 rs3242C>T, rs16890444C>T, sFRP3 c.970C>G, sFRP4 c.958C>A, c.1019G>A, and sFRP5 c.20G>C polymorphisms were analyzed, and bone mineral density (BMD) at the lumbar spine and femoral neck (FN) was measured before and after 1 year of sequential estrogen plus progestogen therapy. Results: The percentage changes in BMD of the FN after 1 year of HT were found to be significantly (P < 0.05) different according to the haplotype genotype composed of the sFRP4 c.958C>A and c.1019G>A polymorphisms after adjustment for baseline BMD. The percentage change in BMD at the FN after 1 year of HT was significantly higher in the AA/AG haplotype genotype than in the AG/CG (P < 0.01) or CG/CG (P < 0.05) haplotype genotype. However, any single and combined polymorphisms measured were not related with nonresponsiveness to HT when a nonresponder was defined as a woman who had lost more than 3% of BMD per year after HT. Conclusions: The haplotype genotypes of sFRP4 c.958C>A and c.1019G>A polymorphisms are genetic factors that affect changes in BMD of the FN after HT in postmenopausal Korean women.