Institute of Gerontology, Liyuan Hospital, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):481-5. doi: 10.1016/j.bbrc.2009.11.084. Epub 2009 Nov 15.
Polymorphisms of G-572C and G-174C in the interleukin-6 (IL-6) promoter can affect both the transcription and secretion of IL-6 and may be involved in inflammation related to and the pathogenesis of ischemic stroke (IS). However, whether IL-6 polymorphisms are indeed risk factors for IS remains controversial. We recruited 748 Chinese IS patients diagnosed by magnetic resonance imaging (MRI) within 24h of symptom onset and 748 normal healthy controls from two ethnic populations and performed two case-control studies in order to assess the nature of the polymorphisms of IL-6 and any links with IS. Common polymorphic loci in the IL-6 gene promoter were determined by TaqMan SNP genotyping assays. Multivariate logistic regression analysis was used to examine the association between IL-6 genotypes and a diagnosis of IS. We found that the C allele frequency at the -174 promoter region of IL-6 was extremely low in both IS patients and controls in both ethnic groups. The G allele of the promoter single nucleotide polymorphism (SNP) G-572C was more common in IS subjects than controls (P=0.004, corrected for multiple testing) in the Han population but not in the Uyghur population. GC carriage therefore increased the risk of IS in the Han ethnic group (OR 1.45, 95% CI 1.13-1.86). In addition, the differences in GG and GC frequency between the two ethnic populations were significant. The C allele frequency at the -174 promoter region of IL-6 was rare in Chinese IS patients and controls from either ethnic group. We conclude that IL-6-572GC may be an independent risk factor for IS in the Chinese Han population.
白细胞介素-6（IL-6）启动子中的 G-572C 和 G-174C 多态性可影响 IL-6 的转录和分泌，可能与缺血性脑卒中（IS）相关的炎症和发病机制有关。然而，IL-6 多态性是否确实是 IS 的危险因素仍存在争议。我们从两个民族群体中招募了 748 名在症状发作后 24 小时内通过磁共振成像（MRI）诊断为 IS 的中国 IS 患者和 748 名正常健康对照者，并进行了两项病例对照研究，以评估 IL-6 多态性的性质及其与 IS 的任何关联。通过 TaqMan SNP 基因分型测定法确定 IL-6 基因启动子中的常见多态性位点。采用多元逻辑回归分析检查 IL-6 基因型与 IS 诊断之间的关联。我们发现，在两个民族群体中，IL-6 启动子区域的-174 位的 C 等位基因频率在 IS 患者和对照者中均极低。汉族 IS 患者中启动子单核苷酸多态性（SNP）G-572C 的 G 等位基因比对照组更常见（P=0.004，经多重检验校正），但在维吾尔族中并非如此。因此，GC 携带增加了汉族 IS 的风险（OR 1.45，95%CI 1.13-1.86）。此外，两个民族群体之间 GG 和 GC 频率的差异具有统计学意义。IL-6-174 启动子区域的 C 等位基因频率在汉族和维吾尔族的中国 IS 患者和对照组中均罕见。我们的结论是，IL-6-572GC 可能是汉族人群 IS 的独立危险因素。
