title: Methylation in the matrix metalloproteinase-2 gene is associated with cerebral ischemic stroke.
abstract: Matrix metalloproteinase-2 (MMP-2) is involved in the pathophysiology of stroke. Previous studies have shown that MMP-2 activity is increased in stroke; however, evidence of epigenetic regulation of the MMP-2 in stroke is still limited. We examined methylation of the MMP-2 promoter in patients with ischemic stroke. This study included 298 patients with ischemic stroke and 258 age-matched and sex-matched controls. MMP-2 promoter methylation levels were measured by pyrosequencing at eight potential cytosine-guanine (CpG) sites. Multivariate regression analysis was used to adjust for general stroke risk factors, and the specific effects of sex and stroke subtype were analysed. The methylation levels of MMP-2 in the peripheral blood of the patients with stroke were lower than controls in all eight CpG sites, especially at site 1, site 5, site 7, and site 8 (adjusted p=0.036, 0.002, 0.021, and 0.041, respectively). In subgroup analysis by sex, a significant association was found only in men but not in women. When the stroke subtype was considered, men with small-vessel stroke had significantly lower methylation levels at all MMP-2 CpG sites than the controls (3.01% vs 3.65%, adjusted p=0.018). Although men with large-artery atherosclerosis stroke also had lower MMP-2 methylation levels, no significant difference was found (3.25% vs 3.65%, adjusted p=0.253). Demethylation of the MMP-2 promoter in patients with ischemic stroke was in a sex and stroke subtype-specific manners. These findings may add to the understanding of epigenetic modification of MMP-2 on ischemic stroke.
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Neurology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsiu-Fen
authors.initials: HF
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Edward
authors.initials: E
authors.lastname: Hsi
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ling-Chun
authors.initials: LC
authors.lastname: Huang
authors.affiliation: Department of Neurology, Taipei Veterans General Hospital, Taipei, Taiwan.|Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.affiliation: Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.|Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.|Institute of New Drug Development, China Medical University, Taichung, Taiwan.
authors.forename: Suh-Hang H
authors.initials: SH
authors.lastname: Juo
authors.affiliation: Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Neurology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ruey-Tay
authors.initials: RT
authors.lastname: Lin
mesh_terms: D002545:Brain Ischemia / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020521:Stroke / Q000150:complications / Q000201:enzymology* / Q000235:genetics*
chemical_list: D020778:Matrix Metalloproteinase 2
keywords: Extracellular Matrix Proteins; Promoter Regions, Genetic; Stroke