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Korean Journal of Bone Metabolism 2005;12(2):203-215.
Association of Double Polymorphisms of the KLOTHO and Osteoprotegerin Genes with Serum Osteoprotegerin Levels and Bone Mineral Density in Korean Women
한국인 성인 여성에서 KLOTHO 및 Osteoprotegerin 이중 유전자 다형성과 혈청 Osteoprotegerin 농도 및 골밀도의 연관성
오기원,윤은주1,이은정2,이원영2,백기현3,한제호3,강무일3,박성우
한림대학교 의과대학 내과학교실, 방사선과학교실1, 성균관대학교 의과대학 내과학교실2, 가톨릭대학교 의과대학 내과학교실3
Abstract
Background
Osteoprotegerin (OPG) is a decoy receptor for the receptor activator of NF-κB ligand and an important inhibitor of osteoclastogenesis. Klotho gene has been identified as a suppressor of aging phenotypes, and knockout mice for klotho gene show low-turnover osteopenia. Recently, klotho and OPG have been proposed as linkage genes between osteoporosis and arterial calcification, but the precise mechanisms are not clear. We investigated the relationships of double polymorphisms of the KLOTHO and OPG gene with serum OPG levels and bone mineral density in healthy Korean women.
Methods
Genotyping were done for polymorphisms of KLOTHO gene, G395A and C1818T, and OPG gene, A163G, G209A, T245G and T950C, in 251 healthy Korean women (mean age, 51.3±6.9 yr) by allelic discrimination using the 5' nuclease polymerase chain reaction assay. Serum OPG levels were measured and bone mineral density (BMD) were examined by standardized methods.
Results
Allelic frequencies of KLOTHO and OPG polymorphisms were in compliance with HardyWeinberg equilibrium and most of the polymorphisms were in linkage disequilibrium. Low serum OPG levels in minor allele carriers of KLOTHO gene showed a tendency for increment by the coexistence of minor allele of OPG gene, although statistically not significant. Analyses in double polymorphisms of the KLOTHO and OPG genes revealed that low BMD vales in minor allele carriers of KLOTHO gene was partly rescued by the coexistence of minor allele of OPG gene.
Conclusion
The OPG gene polymorphism is at least partly responsible for the change of BMD in the minor allele carrier of KLOTHO gene. Further studies are needed to clarify this relationship.
Key Words: KLOTHO, Osteoprotegerin, Polymorphism, Bone mineral density


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