title: TIMP-1 polymorphisms in a Chinese Han population with intracerebral hemorrhage.
abstract: Remodeling of extracellular matrix (ECM) and breakdown of blood-brain barrier (BBB) are crucial events in the pathogenesis of intracerebral hemorrhage (ICH). Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, are the most important degrading enzymes in the ECM and BBB. These proteolytic effects are controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is the main endogenous inhibitor of MMP-9. Two polymorphisms in the TIMP-1 gene (rs4898 and rs2070584) were selected through a literature review and successfully genotyped in a study sample of 410 ICH patients and 305 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined. Furthermore, the serum levels of TIMP-1 were measured in a subgroup of 96 ICH patients on days 1 after ICH onset and 76 controls. Analyses showed that C allele of rs2070584 was significantly associated with the development of ICH in male subjects (p = 0.037, OR = 1.535, 95%CI 1.025-2.300). Multiple logistic regression analysis under three genetic models demonstrated both rs4898 and rs2070584 were not risk factors for ICH in female subjects. Furthermore, serum levels of TIMP-1 were significantly higher in ICH patients than those in normal controls. However, the serum levels of TIMP-1 showed a nonsignificant decrease, depending on the alleles and genotypes of rs2070584 both in male and female cases. In conclusion, this is the first association study of the TIMP-1 gene variants with ICH. Our data suggest that C allele of rs2070584 is a risk factor for ICH development in the Chinese male population. However, the precise function of this variant needs further investigation.
authors.affiliation: 1Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, P. R .China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Wang
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: Yang
authors.forename: Bao-Qiong
authors.initials: BQ
authors.lastname: Liu
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Ma
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Xia
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Xu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Du
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001794:Blood Pressure; D002543:Cerebral Hemorrhage / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012189:Retrospective Studies; D012737:Sex Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1