Biomarkers of inflammation and MRI-defined small vessel disease of the brain - The Cardiovascular Health Study
Biomarkers of inflammation and MRI-defined small vessel disease of the brain - The Cardiovascular Health Study
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DOI：
10.1161/strokeaha.107.508135
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发表时间：
2008-07-01
期刊：
影响因子：
8.3
通讯作者：
Longstreth, W. T., Jr.
中科院分区：
文献类型：
--
作者：
Fornage, Myriam;Chiang, Y. Aron;Longstreth, W. T., Jr.
背景和目的：为了阐明炎症在脑部小血管疾病发病机制中的作用，我们在心血管健康研究的老年参与者中调查了C-反应蛋白(CRP)和白介素6(IL-6)基因的常见变异、血浆CRP和IL6水平与MRI定义的白质病变(WML)和脑梗塞(BI)的相关性。在横断面分析中，建立了校正已知心血管疾病危险因素的Logistic回归模型，以评估在黑人(n=532)和白人(n=2905)中，血浆CRP和IL6水平以及共同的CRP和IL6基因单倍型与WML或BI的关系。在白人中，IL6基因的常见单倍型与WML和BI显著相关。由-174G/C启动子多态性标记的常见单倍型与WML的风险增加相关(OR=1.14；95%CI：[1.02；1.28])。-572G/C启动子多态标记的常见单倍型与BI风险增加相关(OR=1.57；95%CI：[1.15；2.14])。在黑人中，WML或BI与IL6基因变异或任何一个种族中的CRP基因变异都缺乏显著的相关性。结论--本研究为血浆炎症生物标志物与脑部小血管疾病之间的关系提供了遗传学基础的证据。需要进一步的研究来阐明IL6在疾病发病机制中的具体作用。
Background and Purpose - To clarify the role of inflammation in the pathogenesis of small vessel disease of the brain, we investigated the association between common variation in the C-reactive protein (CRP) and interleukin (IL)-6 genes, plasma CRP and IL6 levels, and presence of MRI-defined white matter lesions (WML) and brain infarcts (BI) in elderly participants of the Cardiovascular Health Study.Methods - Tag single nucleotide polymorphisms (SNPs) in the CRP and IL6 genes were selected from the SeattleSNPs database. In cross-sectional analyses, logistic regression models adjusting for known cardiovascular disease risk factors were constructed to assess the associations of plasma CRP and IL6 levels and common CRP and IL6 gene haplotypes with presence of WML or BI in Blacks (n = 532) and Whites (n = 2905).Results - Plasma IL6 and CRP levels were associated with presence of WML and BI in both races. In Whites, common haplotypes of the IL6 gene were significantly associated with WML and BI. The common haplotype tagged by the -174G/ C promoter polymorphism was associated with an increased risk of WML (OR = 1.14; 95% CI: [1.02; 1.28]). The common haplotype tagged by the -572G/ C promoter polymorphism was associated with an increased risk of BI (OR = 1.57; 95% CI: [1.15; 2.14]). Significant associations were lacking for WML or BI with IL6 gene variation in Blacks, or with CRP gene variation in either race.Conclusions - This study provides evidence of a genetic basis underlying the relationship between plasma biomarkers of inflammation and small vessel disease of the brain. Further studies to elucidate the specific role of IL6 in disease pathogenesis are warranted.