Shi Dongquan, Ni Haijian, Dai Jin, Qin Jianghui, Xu Yong, Zhu Lunqing, Yao Chen, Shao Zhenxing, Chen Dongyang, Xu Zhihong, Yi Long, Ikegawa Shiro, Jiang Qing
The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, PR China.
BMC Med Genet. 2008 Oct 22;9:91. doi: 10.1186/1471-2350-9-91.
CALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.
A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.
No significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.
The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.
CALM1基因编码钙调蛋白（CaM），这是一种重要且广泛存在的真核生物Ca2+结合蛋白。多项研究表明，CaM功能缺陷可能参与骨关节炎（OA）的发病机制。一个日本研究团队通过一项令人信服的全基因组关联研究，最近证实了CALM1核心启动子多态性（-16C/T转换单核苷酸多态性，rs12885713）与OA易感性之间存在遗传关联。然而，随后在不同选择人群的OA患者中进行的关联研究未能得出一致结果。本研究旨在评估-16C/T多态性与中国汉族人群膝骨关节炎的相关性。
进行了一项病例对照关联研究。对183例经影像学证实患有原发性症状性膝骨关节炎的患者以及210例匹配的对照进行了该多态性的基因分型。比较了患者和对照受试者之间的等位基因和基因型频率。
膝骨关节炎组与对照组之间在基因型或等位基因分布上未检测到显著差异（所有P>0.05）。即使按性别分层后，该关联也为阴性。此外，在OA患者中未观察到-16C/T单核苷酸多态性基因型与临床变量年龄、性别、体重指数（BMI）和K/L（凯尔格伦/劳伦斯）评分之间存在关联。
本研究表明，CALM1核心启动子多态性-16C/T不是中国汉族人群膝骨关节炎易感性的危险因素。需要进一步研究以全面了解该多态性在OA发病机制中的作用。
