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Korean Journal of Obstetrics & Gynecology 2007;50(6):901-911.
Published online June 1, 2007.
The relationship between osteoprotegerin (OPG)-receptor activator of NF-kB ligand (RANKL) gene polymorphisms and change in bone mineral density after hormone therapy in postmenopausal Korean women.
Jung Gu Kim, Seung Yup Ku, Byung Chul Jee, Chang Suk Suh, Seok Hyun Kim, Young Min Choi, Shin Yong Moon
Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea. kimjg@plaza.snu.ac.kr
To investigate the relationship of polymorphisms in osteoprotegerin (OPG)-receptor activator of NF-kB ligand (RANKL) gene to changes in circulating OPG and soluble RANKL (sRANKL) levels and in bone mineral density (BMD) after hormone therapy (HT) in postmenopausal Korean women. METHODS: The OPG T245G, and G1181C polymorphisms and RANKL rs2277438 A/G polymorphism were analyzed by polymerase chain reaction-restriction fragment length polymorphsim (PCR-RFLP) or direct DNA sequencing in 236 postmenopausal Korean women receiving sequential HT for 1 year. Serum OPG, sRANKL, bone alkaline phosphatase, CrossLaps (CTX), osteocalcin, clacitonin, parathyroid hormone, calicum, and phophorus were measured using enzyme-linked immunosorbent assay (ELISA), immunoassay and atomic absorptiometry respectively. BMD at the lumbar spine and proximal femur was determined by dual energy X-ray absorptiometry. RESULTS: The annual percent changes of BMD were not associated with single or combined genotypes of OPG and RANKL gene polymorphisms, and the distributions of these genotypes were not different between HT-responders and HT-nonresponders (women who lose more than 3% of bone mass per year). After HT of 6 months, change in serum sRANKL levels was significantly higher in GG genotype than in other genotype of RANKL gene polymorphism. No differences in the 6 month changes of other bone turnover markers including circulating OPG levels after HT were noted across single OPG genotype and combined genotypes of OPG and RANKL polymorphisms. CONCLUSIONS: The OPG T245G, and G1181C polymorphisms, and RANKL polymorphism did not associate with change in BMD after HT in postmenopausal Korean women, and RANKL polymorphism affects change in circulating sRANKL levels after HT.
Key Words: OPG, RANKL, Gene polymorphism, BMD, HT

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