Greisenegger Stefan, Endler Georg, Haering Daniela, Schillinger Martin, Lang Wilfried, Lalouschek Wolfgang, Mannhalter Christine
Clinical Department of Clinical Neurology, University of Vienna Medical School, Waehringer Guertel 18-20, 1097 Vienna, Austria.
Thromb Res. 2003 Jun 1;110(4):181-6. doi: 10.1016/s0049-3848(03)00376-1.
Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (-174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60.
We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (-174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time.
In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (-174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale> or =6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (-174)GG genotype was significantly associated with severe disability after 1 week (RS 4-5; odds ratio (OR)=3.2, 95% CI: 1.5-6.6; p=0.002; NIHSS> or =6; OR=4.2, 95% CI: 1.6-11.1).
The (-174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings.
血浆白细胞介素-6（IL-6）水平升高与急性血管事件风险增加及预后较差相关。IL-6基因第（-174）位核苷酸处常见的G/C启动子多态性已被证明会影响基础IL-6水平。因此，IL-6基因型可能与缺血性卒中（IS）的风险及预后相关。我们研究了这种多态性与脑血管事件之间的统计学关联，以及60岁之前出现症状的患者的临床预后。
我们通过诱变分离聚合酶链反应（MS PCR）检测了214例60岁及以下的急性缺血性卒中或短暂性脑缺血发作（TIA）患者以及214例年龄和性别匹配的健康对照者的IL-6基因（-174）G/C多态性。在预定时间点通过经过验证的量表评估血管事件的临床严重程度。
在患者总组中，患者组的基因型和等位基因频率（38% GG，45% GC，17% CC；等位基因频率：60% G，40% C）与对照组无显著差异。然而，（-174）G变异纯合个体在入院时及事件发生后1周的美国国立卫生研究院卒中量表（NIHSS）评分明显更差。此外，事件发生后1周和3个月时严重残疾的患者（改良Rankin量表（RS）评分为4或5；NIHSS≥6）携带GG基因型的比例明显更高。在多变量分析中，IL-6（-174）GG基因型与1周后严重残疾显著相关（RS 4 - 5；优势比（OR）=3.2，95%置信区间：1.5 - 6.6；p = 0.002；NIHSS≥6；OR = 4.2，95%置信区间：1.6 - 11.1）。
IL-6基因的（-174）GG基因型与急性脑血管事件的年轻患者发生严重卒中相关。需要进一步对更大患者群体进行研究以证实这些发现。
