Min Zhang1, Wusheng Zhu2, Wenwei Yun3, Qizhang Wang4, Maogang Cheng5, Zhizhong Zhang2, Xinfeng Liu2, Xianju Zhou6, Gelin Xu7. 1. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China; Department of Neurology, Laboratory of Neurological Diseases, Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China. 2. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China. 3. Department of Neurology, Laboratory of Neurological Diseases, Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China. 4. Department of Neurology, Shenzhen Shajing Hospital, The Affiliated of Guangzhou Medical University, Guangdong Province, China. 5. Department of Neurology, Yancheng City First People's Hospital, The Fourth Affiliated Hospital of Nantong University, Jiangsu Province, China. 6. Department of Neurology, Laboratory of Neurological Diseases, Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China. Electronic address: xianju_zhou@yahoo.com. 7. Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China. Electronic address: gelinxu@gmail.com.cn.
Abstract
BACKGROUND: Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood-brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. METHODS: A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. RESULTS: Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls (P=0.009, χ(2) test; P=0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067-6.364; P=0.036). CONCLUSION: Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA.
BACKGROUND: Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood-brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. METHODS: A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVDpatients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. RESULTS: Of 178 SVDpatients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVDpatients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls (P=0.009, χ(2) test; P=0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067-6.364; P=0.036). CONCLUSION: Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA.
Authors: Dao Pei Zhang; Yan Fang Peng; Huai Liang Zhang; Jian Gong Ma; Min Zhao; Suo Yin; Tian Tian Wei Journal: Front Neurosci Date: 2019-08-14 Impact factor: 4.677