Rhee Eun Jung, Oh Ki Won, Jung Chan Hee, Lee Won Young, Oh Eun Sook, Yun Eun Joo, Baek Ki Hyun, Kang Moo Il, Kim Sun Woo
Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
Clin Endocrinol (Oxf). 2006 Jun;64(6):689-97. doi: 10.1111/j.1365-2265.2006.02530.x.
Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of the NF-kappaB ligand (RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. OPG has been proposed as a link molecule between osteoporosis and arterial calcification, but the relationship between the OPG gene and the cardiovascular system in human populations is unclear. Thus, the aim of this study was to investigate the relationship between OPG gene polymorphisms and aortic calcification or coronary artery disease in Koreans.
Genotyping of four polymorphisms, A163G, G209A, T245G and T950C, in the promoter region of the OPG gene was performed in 251 healthy Korean women (mean age 51.3 +/- 6.9 years) and in a second study population consisting of 100 patients who underwent coronary angiography (mean age 57.0 +/- 11.9 years), by allelic discrimination using the 5' nuclease polymerase chain reaction assay. Cardiovascular risk factors and serum OPG levels were measured and aortic calcification in thoracic and abdominal aorta was examined by simple radiological methods.
In the first study population, the prevalence of aortic calcification increased significantly as the subjects grew older. The frequencies of mutant alleles were significantly higher in the subjects with aortic calcification compared with those without aortic calcification in G209A and T950C polymorphisms, although these significances were lost after adjustment for age. No significant relationship was found between OPG gene polymorphisms and serum OPG levels or cardiovascular risk factors. In the second study group, there were no associations between OPG promoter genotypes and aortic calcification, serum OPG levels, or coronary artery disease.
We observed that the four polymorphisms in the promoter region of the OPG gene were not associated with aortic calcification or coronary artery disease in Koreans. Further studies are needed to clarify this relationship.
骨保护素（OPG）是最近发现的一种细胞因子，它作为核因子κB受体活化因子配体（RANKL）的诱饵受体发挥作用。在动物模型中，OPG已被证明是破骨细胞生成和动脉钙化的重要抑制剂。OPG被认为是骨质疏松症和动脉钙化之间的连接分子，但在人群中OPG基因与心血管系统之间的关系尚不清楚。因此，本研究的目的是调查韩国人群中OPG基因多态性与主动脉钙化或冠状动脉疾病之间的关系。
采用5'核酸酶聚合酶链反应分析法进行等位基因鉴别，对251名健康韩国女性（平均年龄51.3±6.9岁）以及由100名接受冠状动脉造影检查的患者（平均年龄57.0±11.9岁）组成的第二个研究群体，进行OPG基因启动子区域四个多态性位点A163G、G209A、T245G和T950C的基因分型。测量心血管危险因素和血清OPG水平，并通过简单的放射学方法检查胸主动脉和腹主动脉的钙化情况。
在第一个研究群体中，主动脉钙化的患病率随受试者年龄增长而显著增加。在G209A和T950C多态性中，有主动脉钙化的受试者突变等位基因频率显著高于无主动脉钙化者，尽管在调整年龄后这些显著性消失。未发现OPG基因多态性与血清OPG水平或心血管危险因素之间存在显著关系。在第二个研究组中，OPG启动子基因型与主动脉钙化、血清OPG水平或冠状动脉疾病之间无关联。
我们观察到韩国人群中OPG基因启动子区域的四个多态性与主动脉钙化或冠状动脉疾病无关。需要进一步研究来阐明这种关系。
