MMP9 rs17576 同时与中国人群的症状性颅内动脉粥样硬化狭窄和脑白质高信号相关。
MMP9 rs17576 Is Simultaneously Correlated with Symptomatic Intracranial Atherosclerotic Stenosis and White Matter Hyperintensities in Chinese Population.
机构信息
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
出版信息
Cerebrovasc Dis. 2021;50(1):4-11. doi: 10.1159/000511582. Epub 2020 Dec 9.
PURPOSE
The aim of this study was screening for single nucleotide polymorphisms (SNPs) associated with white matter hyperintensities (WMHs) in symptomatic intracranial atherosclerotic stenosis (sICAS) patients and exploring a possible connection in the genetic background between macrovascular disease and small vessel disease.
METHODS
There were 400 sICAS patients enrolled in the study. Fazekas scores were applied to WMH classification. Healthy controls were referred to 1,000 Genome Project and GeneSky company who provided 1,007 Chinese healthy controls. Fast target sequencing technology was used to select the SNPs of 102 genes related to the pathogenesis of sICAS in the sICAS patients.
RESULTS
The allele frequencies of 88 SNPs were significantly different between the sICAS group and the healthy controls (p < 0.05). The allele frequencies of 53 SNPs were significantly different between the sICAS patients with and without WMHs (p < 0.05). Further analysis found that matrix metalloproteinase 9 (MMP9) rs17576 was simultaneously related to sICAS and WMHs. The frequency of the rs17576 A allele was significantly lower in sICAS patients when compared to the normal controls (p = 0.03, OR [95% CI] = 0.75 [0.625-0.91]). Also, the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.009), dominant (p = 0.014), and recessive (p= 0.023) models. The frequency of the rs17576 A allele was significantly higher in sICAS with WMH patients, compared to those without WMHs (p = 0.022, OR [95% CI] = 1.54 [1.06-2.22]); the frequency of the rs17576 genotypes was significantly different under codominant (p = 0.019) and recessive (p = 0.032) models. Logistic regression analysis showed that age, hypertension, and MMP9 rs17576 AA genotype were independent risk factors for sICAS with WMHs.
CONCLUSION
MMP9 rs17576 may be simultaneously associated with the risk of sICAS and WMHs.
目的
本研究旨在筛选与症状性颅内动脉粥样硬化狭窄（sICAS）患者脑白质高信号（WMHs）相关的单核苷酸多态性（SNPs），并探讨大血管疾病和小血管疾病之间遗传背景的可能联系。
方法
共纳入 400 例 sICAS 患者，采用 Fazekas 评分对 WMH 进行分类。健康对照组为 1000 基因组计划和基因天空公司的 1007 名中国健康对照者。采用快速靶向测序技术，在 sICAS 患者中选择与 sICAS 发病机制相关的 102 个基因的 SNPs。
结果
sICAS 组与健康对照组之间 88 个 SNPs 的等位基因频率差异有统计学意义（p<0.05）。sICAS 患者有和无 WMHs 之间 53 个 SNPs 的等位基因频率差异有统计学意义（p<0.05）。进一步分析发现，基质金属蛋白酶 9（MMP9）rs17576 同时与 sICAS 和 WMHs 相关。与正常对照组相比，sICAS 患者 rs17576A 等位基因频率明显降低（p=0.03，OR[95%CI]=0.75[0.625-0.91]）。同样，在共显性（p=0.009）、显性（p=0.014）和隐性（p=0.023）模型下，rs17576 基因型的频率差异有统计学意义。与无 WMHs 的 sICAS 患者相比，伴有 WMHs 的 sICAS 患者 rs17576A 等位基因频率明显升高（p=0.022，OR[95%CI]=1.54[1.06-2.22]）；在共显性（p=0.019）和隐性（p=0.032）模型下，rs17576 基因型的频率差异有统计学意义。Logistic 回归分析显示，年龄、高血压和 MMP9 rs17576AA 基因型是伴有 WMHs 的 sICAS 的独立危险因素。
结论
MMP9 rs17576 可能同时与 sICAS 和 WMHs 的风险相关。
Zotero 插件