TIMP-1 polymorphisms in a Chinese Han population with intracerebral hemorrhage

Int J Neurosci. 2014 Jan;124(1):61-7. doi: 10.3109/00207454.2013.823604. Epub 2013 Aug 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / ethnology
  • Asian People / genetics
  • Blood Pressure
  • Cerebral Hemorrhage / blood
  • Cerebral Hemorrhage / ethnology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / physiopathology
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Regression Analysis
  • Retrospective Studies
  • Sex Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*

Substances

  • Tissue Inhibitor of Metalloproteinase-1