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.

Association of TIMP-1 and COL4A4 Gene Polymorphisms with Keratoconus in an Iranian Population

“…[14,22,30,31] TIMP-1 gene rs4898 (+372C/T) (HGVM6380940) is located within the intron of the synapsin gene, and single nucleotide polymorphism (SNP) is located in exon 5, the region of NM_006950.3. Some studies investigated the association of rs4898 gene polymorphism with disorders including intracerebral hemorrhage, [32] systemic sclerosis, [33] and severe sepsis. [34] The present study aimed to evaluate the possible association of TIMP-1 rs4898 C/T gene polymorphism and COL4A4 rs2228557 C/T gene polymorphism with the development of KC in a sample of Iranian population.…”

Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis

“…Within 24 h of having a stroke, the expression level of CXCL1 in the cerebrospinal fluid of patients positively correlates with the ischemic area, indicating that CXCL1 may participate in the regulation of brain tissue damage (Losy, Zaremba & Skrobanski, 2005). The abnormal expression of TIMP1 can disrupt the integrity of the blood–brain barrier and this disruption may be involved in the regulation of the pathological process of ICH (Wang et al, 2014a). The urokinase-type plasminogen activator, encoded by the PLAUR gene, is involved in the development of the neural circuit of the cortex and in brain tissue remodeling after a brain injury (Levi et al, 2001).…”

Peer Review #1 of "Identification of hub genes and small-molecule compounds related to intracerebral hemorrhage with bioinformatics analysis (v0.2)"

“…Within 24 hours of having a stroke, the expression level of CXCL1 in the cerebrospinal fluid of patients positively correlates with the ischemic area, indicating that CXCL1 may participate in the regulation of brain tissue damage (Losy et al 2005). The abnormal expression of TIMP1 can disrupt the integrity of the blood-brain barrier and this disruption may be involved in the regulation of the pathological process of ICH (Wang et al 2014a). The urokinase-type plasminogen activator, encoded by the PLAUR gene, is involved in the development of the neural circuit of the cortex and in brain tissue remodeling after a brain injury (Levi et al 2001).…”