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

Kim, Hoon MD, PhD1; Lee, Dong Ock MD2; Ku, Seung-Yup MD, PhD3,4; Kim, Seok Hyun MD, PhD3,4; Kim, Jong Hak MD, PhD5; Kim, Jung Gu MD, PhD3,4

doi: 10.1097/gme.0b013e3182503d47
Original Articles

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.

From the 1Department of Obstetrics and Gynecology, Incheon Medical Center, Incheon, Korea; 2Department of Obstetrics and Gynecology, National Cancer Center, Koyang, Korea; 3Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Korea; 4Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; and 5Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.

Received November 21, 2011; revised and accepted January 10, 2012.

Funding/support: This study was supported by a grant (A080012) from the Korea Health technology R&D project, Ministry of Health, Welfare & Family Affairs, Republic of Korea.

Financial disclosure/conflicts of interest: None reported.

J.H.K. and J.G.K. contributed equally to this work as corresponding authors.

Address correspondence to: Jung Gu Kim, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yeungun-dong, Chongno-gu, Seoul 110-744, Korea. E-mail: kimjg@plaza.snu.ac.kr; Jong Hak Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Ewha Womans University Mokdong Hospital, 911, Mok-dong, Yangcheon-gu, Seoul 158-710, Korea. E-mail: kjhanes@ewha.ac.kr

©2012The North American Menopause Society