Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
J Cardiol. 2009 Aug;54(1):66-70. doi: 10.1016/j.jjcc.2009.04.001. Epub 2009 May 13.
The cytotoxic action of leukocytes is known to be a probable cause of the cardiac myocyte damage seen in idiopathic dilated cardiomyopathy (IDC). Monocyte chemoattractant protein 1 (MCP-1) contributes to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. MCP-1 has been reported to be dynamically regulated in IDC and may contribute to the deterioration of left ventricular function. In addition, a polymorphism at -2518 (G/A) in the MCP-1 gene affects the level of MCP-1 expression in response to an inflammatory stimulus.
We genotyped the polymorphism at -2518 G/A in the MCP-1 gene in 73 Japanese patients with nonfamilial IDC and 349 healthy controls. The distribution of the MCP-1 genotypes in the IDC patients differed significantly from the controls (p=0.016). In a dominant G allele model, there was a significant difference in the distribution of genotypes between the two groups (p<0.01). The odds ratio for nonfamilial IDC associated with the GG vs. non-GG genotype was 10.4 (95% CI=1.7-64.5) after adjustment for the confounding factors.
These findings suggest that the G allele at -2518 in the MCP-1 gene may be a novel genetic marker of susceptibility to nonfamilial IDC.
已知白细胞的细胞毒性作用可能是特发性扩张型心肌病（IDC）中心肌细胞损伤的一个原因。单核细胞趋化蛋白 1（MCP-1）有助于增强白细胞的募集和激活，导致心肌细胞的慢性损伤。据报道，MCP-1 在 IDC 中呈动态调节，可能导致左心室功能恶化。此外，MCP-1 基因-2518 位（G/A）的多态性影响对炎症刺激的 MCP-1 表达水平。
我们对 73 名非家族性 IDC 日本患者和 349 名健康对照者的 MCP-1 基因-2518 G/A 多态性进行了基因分型。IDC 患者的 MCP-1 基因型分布与对照组有显著差异（p=0.016）。在显性 G 等位基因模型中，两组间基因型分布有显著差异（p<0.01）。在调整混杂因素后，与非-GG 基因型相比，与 GG 基因型相关的非家族性 IDC 的优势比为 10.4（95%CI=1.7-64.5）。
这些发现表明，MCP-1 基因-2518 位的 G 等位基因可能是非家族性 IDC 的一个新的遗传易感性标志物。
