Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
CNS Neurosci Ther. 2013 Oct;19(10):785-94. doi: 10.1111/cns.12136. Epub 2013 Jun 15.
Dysregulation of the activity of the disintegrin/metalloproteinase ADAM10 could contribute to the development of atherosclerosis. Although a number of genetic studies have focused on the association of ADAM10 gene polymorphisms with susceptibility to diseases, no genetic association studies of ADAM10 gene variability with atherosclerotic cerebral infarction (ACI) have been conducted. The aim of this study was to analyze the potential association between ADAM10 promoter polymorphisms and ACI.
The associations between rs653765 and rs514049 polymorphisms of the ADAM10 promoter and the possible risk of ACI were assessed among 347 patients with ACI and 299 matched healthy individuals in a case-control study.
Overall, there was a significant difference in the genotypes frequencies of rs653765 (P = 0.04) between the ACI and control subjects. In addition, the rs653765 mutated allele of ADAM10 was significantly associated with increased ADAM10 expression in patients with ACI (P = 0.032). In contrast, the allele frequency of rs514049 was not statistically associated with ACI, and the rs514049 variant A > C did not affect the expression of ADAM10 either.
Our findings indicate a positive association between the rs653765 polymorphism of ADAM10 and ACI, as well as a negative result for rs514049. In addition, a significant increase in ADAM10 expression was observed in patients with ACI carrying the rs653765 C > T mutation. This new knowledge about ADAM10 might be clinically important and confirm a role for ADAM10 in the pathophysiology of ACI, with potentially important therapeutic implications.
去整合素金属蛋白酶 10（ADAM10）活性失调可能导致动脉粥样硬化的发生。虽然许多遗传研究集中在 ADAM10 基因多态性与疾病易感性的关联上，但尚未进行 ADAM10 基因变异性与动脉粥样硬化性脑梗死（ACI）的遗传关联研究。本研究旨在分析 ADAM10 启动子多态性与 ACI 的潜在关联。
在病例对照研究中，评估了 347 例 ACI 患者和 299 例匹配的健康个体中 ADAM10 启动子 rs653765 和 rs514049 多态性与 ACI 可能风险之间的关联。
总体而言，ACI 组和对照组之间 rs653765 的基因型频率存在显著差异（P = 0.04）。此外，ACI 患者中 ADAM10 的 rs653765 突变等位基因与 ADAM10 表达增加显著相关（P = 0.032）。相反，rs514049 的等位基因频率与 ACI 无统计学关联，rs514049 变异 A > C 也不影响 ADAM10 的表达。
我们的研究结果表明，ADAM10 的 rs653765 多态性与 ACI 之间存在正相关，而 rs514049 则无相关性。此外，携带 rs653765 C > T 突变的 ACI 患者 ADAM10 表达显著增加。关于 ADAM10 的这一新知识可能具有重要的临床意义，并证实 ADAM10 在 ACI 病理生理学中的作用，具有潜在的重要治疗意义。
