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.