Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
Mol Biol Rep. 2012 Sep;39(9):9023-30. doi: 10.1007/s11033-012-1773-y. Epub 2012 Jul 3.
Coronary artery disease (CAD) was the second leading cause of death during the last 3 years in Taiwan. Smooth muscle cells, monocytes/macrophages, and endothelial cells produce monocyte chemoattractant protein-1 (MCP-1) within atherosclerotic plaques following binding to the chemokine receptor-2 (CCR-2). Previous studies have well-documented the association between MCP-1 expression and susceptibility to, or clinicopathological features, of CAD. This study investigated the relationships between MCP-1-2518A/G and CCR-2-V64I genetic polymorphisms and CAD in the Taiwanese population. A total of 608 subjects, including 392 non-CAD controls and 216 patients with CAD, were recruited and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to evaluate the effects of these two polymorphic variants on CAD. Results indicated a significant association between MCP-1 -2548 gene polymorphism and susceptibility to CAD. GG genotypes (OR = 1.629; 95 % CI = 1.003-2.644), or individuals with at least one G allele (OR = 1.511; 95 % CI = 1.006-2.270), had a higher risk of CAD as compared with AA genotypes. Results also revealed that subjects with at least one A allele of the V64I CCR2 gene polymorphism had significantly increased risk of CAD. G allele in MCP-1-2518 might contribute to higher prevalence of atrial fibrillation in CAD patients (OR = 4.254; p < 0.05). In conclusion, MCP-1-2518G and CCR-2 64I gene polymorphisms represent important factors in determining susceptibility to CAD, and the contribution of MCP-1-2518G could be through effects on atrial fibrillation in CAD patients.
冠状动脉疾病(CAD)是过去 3 年在台湾的第二大死亡原因。动脉粥样硬化斑块内的平滑肌细胞、单核细胞/巨噬细胞和内皮细胞在与趋化因子受体-2(CCR-2)结合后产生单核细胞趋化蛋白-1(MCP-1)。先前的研究已经充分证明了 MCP-1 表达与 CAD 的易感性或临床病理特征之间的关系。本研究调查了 MCP-1-2518A/G 和 CCR-2-V64I 遗传多态性与台湾人群 CAD 之间的关系。共招募了 608 名受试者,包括 392 名非 CAD 对照组和 216 名 CAD 患者,并进行聚合酶链反应-限制性片段长度多态性(PCR-RFLP)以评估这两种多态变体对 CAD 的影响。结果表明,MCP-1-2548 基因多态性与 CAD 的易感性之间存在显著关联。GG 基因型(OR=1.629;95%CI=1.003-2.644)或至少携带一个 G 等位基因的个体(OR=1.511;95%CI=1.006-2.270)患 CAD 的风险更高与 AA 基因型相比。结果还表明,至少携带一个 V64I CCR2 基因多态性 A 等位基因的个体患 CAD 的风险显著增加。MCP-1-2518 中的 G 等位基因可能导致 CAD 患者心房颤动的患病率更高(OR=4.254;p<0.05)。总之,MCP-1-2518G 和 CCR-264I 基因多态性是决定 CAD 易感性的重要因素,MCP-1-2518G 的贡献可能是通过对 CAD 患者心房颤动的影响。