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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

Menopause:
doi: 10.1097/gme.0b013e3182503d47
Original Articles
Abstract

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.

Author Information

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