Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women

Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women
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DOI:
10.1097/gme.0b013e31802d976f
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发表时间:
2007-09-01
影响因子:
2.7
通讯作者:
Choi, Young Min
Choi, Young Min
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Jung Gu;Kim, Jung Hwa;Choi, Young Min

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目的:探讨韩国绝经后妇女骨保护素(OPG)、核因子kb受体激活因子(RANK)和RANK配体(RANKL)基因多态性与循环OPG、可溶性RANKL (sRANKL)水平和骨密度(BMD)的关系。设计:分析385名韩国绝经后妇女的OPG基因A163G、G209A、T245G和G1181C多态性,RANK基因C421T和C575T多态性,RANKL基因rs12721445和rs2277438多态性。测定血清OPG、可溶性RANKL、骨钙素、I型胶原c端肽、甲状旁腺激素、钙、磷水平和腰椎、股骨颈骨密度。结果:OPG基因的A163G、G209A和T245G多态性为完全连锁。未观察到RANK C421T和C575T多态性和RANKL rs12711445多态性。仅发现OPG G 1181 C多态性与骨密度相关,CC基因型女性腰椎骨密度显著高于GC或GG基因型女性,存在C等位基因剂量效应。RANKL rs2277438多态性本身与BMD无关,但通过将RANKL基因型与OPG G1181C多态性的GC基因型相结合,与腰椎BMD的相关性变得显著。在这些多态性的基因型中,没有发现任何生化标记的水平有显著差异。结论:OPG基因G1181 C多态性,单独或联合RANKL rs2277438多态性,被确定为与韩国女性腰椎骨密度相关的遗传因素。
Objective: To investigate the association between osteoprotegerin (OPG), receptor activator of nuclear factor-KB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL (sRANKL) levels, and bone mineral density (BMD) in Korean postmenopausal women.Design: The OPG gene A163G, G209A, T245G, and G1181C polymorphisms, the RANK gene C421T and C575T polymorphisms, and the RANKL rs12721445 and rs2277438 polymorphisms were analyzed in 385 Korean postmenopausal women. Levels of serum OPG, soluble RANKL, osteocalcin, C-telopeptide of type I collagen, parathyroid hormone, calcium, and phosphorus and BMD at the lumbar spine and femoral neck were measured.Results: The A163G, G209A, and T245G polymorphisms in the OPG gene were in complete linkage. The RANK C421T and C575T polymorphisms and the RANKL rs12711445 polymorphism were not observed. An association with BMD was found only for the OPG G 1181 C polymorphism, and BMD at the lumbar spine in women with the CC genotype was significantly higher than in women with the GC or GG genotype, with a C allele dose effect. In itself, the RANKL rs2277438 polymorphism was not related to BMD, but by combining the RANKL genotypes with the GC genotypes of the OPG G1181C polymorphism, the association with BMD at the lumbar spine became significant. No significant differences in the levels of any biochemical marker among genotypes of these polymorphisms were found.Conclusions: The OPG gene G1181 C polymorphism, alone and in combination with the RANKL rs2277438 polymorphism, was identified as a genetic factor associated with BMD of the lumbar spine in Korean women.