Iacoviello L, Di Castelnuovo A, Gattone M, Pezzini A, Assanelli D, Lorenzet R, Del Zotto E, Colombo M, Napoleone E, Amore C, D'Orazio A, Padovani A, de Gaetano G, Giannuzzi P, Donati M B
Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):222-7. doi: 10.1161/01.ATV.0000150039.60906.02. Epub 2004 Nov 11.
To investigate the role of interleukin-1beta (IL-1beta) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age.
A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the -511C/T IL-1beta polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (P=0.0020 in MI; P=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1beta and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1beta during cell stimulation resulted in a marked reduction of tissue factor activity expression.
-511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
研究白细胞介素-1β（IL-1β）基因多态性在炎症、凝血与青年缺血性血管疾病风险之间的联系中所起的作用。
共研究了406例青年心肌梗死（MI）患者，按年龄、性别和招募中心进行频率匹配，有419例基于人群的健康对照；以及134例青年缺血性中风患者，按年龄和性别匹配，有134例基于人群的健康对照。在对传统危险因素进行校正后，携带-511C/T IL-1β多态性TT基因型的受试者发生MI的风险降低（比值比[OR]，0.36；95%可信区间[CI]，0.20至0.64），发生中风的风险也降低（OR，0.32；95%CI，0.13至0.81）。在两项研究中，T等位基因均显示共显性效应（MI中P = 0.0020；中风中P = 0.021）。与CC纯合子相比，携带T等位基因的志愿者的单核细胞在脂多糖刺激后IL-1β释放减少，组织因子表达降低。在细胞刺激过程中存在抗IL-1β单克隆抗体可导致组织因子活性表达显著降低。
-511C/T IL-1β基因多态性影响青年MI和缺血性中风的风险以及单核细胞对炎症刺激的反应。
