Details

Autor(en) / Beteiligte

• Wang, Hong-Xing
• Yang, Qi-Dong
• Liu, Bao-Qiong
• Zhang, Le
• Ma, Ming-Ming
• Hu, Zhong-Yang
• Xia, Jian
• Xu, Hong-Wei
• Du, Xiao-Ping

Titel

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

Ist Teil von

• International journal of neuroscience, 2014-01, Vol.124 (1), p.61-67

Ort / Verlag

England: Informa Healthcare

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• 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.