Department of Neurology, Helios Klinikum Schleswig, Schleswig, Germany,
Institute of Biometry and Clinical Epidemiology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Cerebrovasc Dis. 2020;49(2):170-176. doi: 10.1159/000507042. Epub 2020 Mar 25.
A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk.
In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor β1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens).
Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects.
A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.
多种炎症基因可能会增加中风风险。我们研究了是否存在更多炎症基因变异与缺血性中风风险相关，以及其他风险因素是否会进一步增加这种风险。
在一项包含 470 例缺血性中风患者（病例）和 807 名对照人群的病例对照研究中，我们检测了 16 个炎症基因（白细胞介素[IL]1A、IL1B、IL1 受体拮抗剂、IL6、IL6 受体、IL10、肿瘤坏死因子-α；C 型趋化因子配体 2、C 型趋化因子受体 5、C 反应蛋白（CRP）、细胞间黏附分子 1、转化生长因子-β1、E-选择素、硒蛋白 S、簇分化抗原 14、组蛋白去乙酰化酶 9[HDAC9]）中的 23 个单倍型或等位基因。我们构建了一个扩展基因评分（EGS），即所有个体风险等位基因的总和，并分析了其对中风的影响，以及其与心血管危险因素和感染评分（针对 5 种微生物抗原的 IgG 抗体和针对 4 种微生物抗原的 IgA 抗体）的关联和交互作用。
与对照组相比，病例组携带白细胞介素 10 rs1800872 基因的次要等位基因的可能性较小，而携带 HDAC9 等位基因 rs11984041 和 CRP 促炎单倍型的可能性较大，但在我们的研究中后者无统计学意义。总体而言，病例组的促炎等位基因和单倍型数量略高于对照组（平均值±标准差分别为 13.25±2.25 和 13.04±2.41）。然而，EGS 仅略微但无统计学意义地增加了中风的风险（OR 1.04，95%CI 0.99-1.09）。其作用与纳入的危险因素无关，也与 IgA 和 IgG 感染评分无关，且未发现显著的交互作用。
炎症基因谱更具促炎特性可能会在一定程度上增加中风风险。这种潜在的影响很可能独立于已确定的心血管危险因素和个体的感染负担。
