Pola Roberto, Flex Andrea, Gaetani Eleonora, Flore Roberto, Serricchio Michele, Pola Paolo
Laboratory of Vascular Biology and Genetics, Department of Geriatric Medicine, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy.
Stroke. 2003 Apr;34(4):881-5. doi: 10.1161/01.STR.0000062346.70983.DF. Epub 2003 Mar 13.
Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) are involved in the pathogenetic mechanisms responsible for several ischemic cardiovascular disorders, including cerebral ischemia. IL-6 and ICAM-1 plasma levels and/or function may be genetically influenced. We sought to evaluate distribution and reciprocal interaction of IL-6 G/C gene promoter polymorphism and ICAM-1 E/K gene polymorphism in Italian patients with history of ischemic stroke.
One hundred nineteen patients with history of ischemic stroke and 133 age- and sex-matched controls were studied. IL-6 and ICAM-1 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis.
The GG genotype of -174 IL-6 G/C gene polymorphism was significantly associated with history of ischemic stroke at both univariate (P<0.0001) and multivariate analysis (odds ratio [OR], 8.6; P<0.0001). Additionally, the EE genotype of ICAM-1 E/K gene polymorphism was significantly more common in the group of patients with history of ischemic stroke (P=0.003) and was an independent variable associated with stroke history (OR, 4.0; P=0.002). Interestingly, a further increased risk of stroke was found in subjects who concomitantly carry the IL-6 GG and ICAM-1 EE genotypes (IL-6 GG/ICAM-1 EE double-homozygous subjects) (OR, 10.1; P=0.004).
There is a synergistic effect of IL-6 G/C and ICAM-1 E/K gene polymorphisms in patients with stroke history. Reciprocal interactions between genotypes may contribute in determining the risk profile for cardiovascular diseases and may merit further investigation as potential therapeutic targets.
白细胞介素-6（IL-6）和细胞间黏附分子-1（ICAM-1）参与了包括脑缺血在内的多种缺血性心血管疾病的发病机制。IL-6和ICAM-1的血浆水平和/或功能可能受遗传因素影响。我们旨在评估意大利有缺血性中风病史患者中IL-6 G/C基因启动子多态性和ICAM-1 E/K基因多态性的分布及相互作用。
研究了119例有缺血性中风病史的患者以及133例年龄和性别匹配的对照者。通过聚合酶链反应和限制性酶切分析评估IL-6和ICAM-1的基因型。
-174 IL-6 G/C基因多态性的GG基因型在单因素分析（P<0.0001）和多因素分析（优势比[OR]，8.6；P<0.0001）中均与缺血性中风病史显著相关。此外，ICAM-1 E/K基因多态性的EE基因型在有缺血性中风病史的患者组中显著更常见（P=0.003），并且是与中风病史相关的独立变量（OR，4.0；P=0.002）。有趣的是，同时携带IL-6 GG和ICAM-1 EE基因型的受试者（IL-6 GG/ICAM-1 EE双纯合子受试者）中风风险进一步增加（OR，10.1；P=0.004）。
IL-6 G/C和ICAM-1 E/K基因多态性在有中风病史的患者中存在协同作用。基因型之间的相互作用可能有助于确定心血管疾病的风险状况，作为潜在的治疗靶点可能值得进一步研究。
