Association of TIMP-1 and TIMP-2 Gene Polymorphisms with Progression of Liver Fibrosis in Patients with Type C Chronic Liver Disease

Ikebuchi, Yuichiro; Ishida, Chihiro; Okamoto, Kinya; Murawaki, Yoshikazu

doi:10.1007/s10528-013-9587-8

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…[49] Furthermore, it was found that among cirrhotic patients, males with TIMP-1 (372C/T) T allele developed cirrhosis at a younger age. [50] Our findings indicated that TIMP-1 (rs4898) was associated with the clinical characteristics of KC only in our male sample population. Nevertheless, the analysis of genotype and allele frequencies revealed no significant differences in female patients as compared to female controls.…”

Section: Discussionmentioning

confidence: 56%

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

Yari¹,

Ehsanbakhsh²,

Validad³

et al. 2020

JOVR

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Purpose: Keratoconus (KC) is a bilateral and noninflammatory disease, characterized by progressive thinning and anterior protrusion of the cornea and may result in severe visual impairment due to irregular astigmatism. Matrix metalloproteinases (MMP) are the main group of enzymes that degrade extracellular matrix proteins including collagens; Type IV collagen is found in the corneal stroma. MMP enzymatic activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). A decrease in TIMP-1 level is associated with the development of KC. In the present study, we investigated the impact of COL4A4 rs2228557 C/T and TIMP-1 rs4898 C/T (X-chromosome) variants on the odds of KC development in a sample of Iranian population. Methods: This case–control study was conducted on 140 patients with KC and 150 healthy control subjects. We used modified methods of Nested-PCR and ARMS-PCR in combination (Nested- ARMS-PCR) and confirmed their validity with RFLP–PCR. Results: Significant differences were noticed between KC patients and healthy individuals regarding the genotype TY or T allele frequencies of rs4898 in the male subjects (OR = 0.43, 95%CI: 0.20–0.92, P = 0.03), whereas no significant differences were identified in the female subjects (OR = 1.07, 95%CI: 0.52–2.20, P = 0.85). The rs2228557, T allele was associated with KC (OR = 0.69, 95% CI: 0.50–0.97, P = 0.035). Conclusion: In the rs2228557 variant, T allele acts as a protective factor from the disease and decreases the risk of KC compared with the C allele. Also, in our investigation about rs4898, we found that TY genotype or T allele decreased the risk of KC compared with the C allele in males and was a protective factor for KC in our population.

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Section: Discussionmentioning

confidence: 56%

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

Yari¹,

Ehsanbakhsh²,

Validad³

et al. 2020

JOVR

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“…Many researchers have focused on TIMP-1 and TIMP-2 during liver regeneration [25][26][27][28] . Some researchers have focused on postoperative behavior of TIMP-1 [28] .…”

Section: Survival Ratementioning

confidence: 99%

“…Currently, four members have been identified in the TIMP family which can inhibit various MMPs [24] . In particular, many researchers have focused on TIMP-1 and TIMP-2 during liver regeneration [25][26][27][28] . Although shear stress with portal hypertension and CIWR injury trigger the liver regeneration cascade after liver surgery, these injuries also cause fatal liver damage [29][30][31] .…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

Hori¹,

Üemoto²,

Chen³

et al. 2014

WJH

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AIM:To investigate oxidative stress (OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver damage. METHODS:Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant (60% hepatectomy); orthotopic liver transplantation (OLT) with whole liver graft (100% OLT); and split OLT (SOLT) with 40% graft (40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OSinduced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase (PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography. RESULTS:Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT. CONCLUSION: Under conditions with an insufficient liver remnant, prevention of OS-induced damage viathe Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery. Hori T et al . Hepatic damage after liver surgeryCore tip: Although shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery, these injuries also cause fatal liver damage. Postoperative liver damage is still a critical matter in the field of liver surgery. Oxidative stress and extracellular matrices are important for liver regeneration after surgery and these may be important keys to overcome current problems in the field of liver surgery. Here, we investigated oxidative stress-mediated damage and the behavior of extracellular matrices in various rat models with liver surgery.Hori T, Uemoto S, Chen F, Gardner LB, Baine AMT, Hata T, Kogure T, Nguyen JH. ��idative stress and e�tracellular ma��idative stress and e�tracellular matrices after hepatectomy and liver transplantation in rats. World

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“…We previously studied the relationships between HCV-related chronic liver disease progression and the presence of functional single-nucleotide polymorphisms (SNPs) of inflammatory cytokines (interleukin-1 beta (IL-1β), an IL-1 receptor antagonist and IL-10), TGF-β, matrix metalloproteinases (MMP-1, -2, -3, -7 and -9) and tissue inhibitors of MMPs (TIMP-1 and -2). Many of these SNPs are associated with liver fibrosis and the development and prognosis of HCC, at least in part (9)(10)(11)(12)(13). Recent reports have shown that various fibrosis-related cytokines and MMPs interact with CTGF.…”

Section: Introductionmentioning

confidence: 99%

Association between Gene Polymorphisms of Connective Tissue Growth Factor and the Progression of Chronic Liver Disease Associated with Hepatitis C

et al. 2014

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Objective Fibrogenic cytokines, such as transforming growth factor-beta 1 play a central role in the progression of liver fibrosis. Recently, functional gene polymorphisms in these cytokines have been identified, and some reports have validated the presence of associations between these polymorphisms and disease progression. Connective tissue growth factor (CTGF) is a stimulating factor for fibroblast proliferation and matrix production. This study aimed to examine the relationship between CTGF gene polymorphisms and the progression of hepatitis C virus (HCV)-related chronic liver disease, as well as the incidence and prognosis of hepatocellular carcinoma (HCC). Methods A review was conducted among 235 HCV patients (117 patients with chronic hepatitis (CH) and 118 patients with liver cirrhosis (LC)). The CTGF gene polymorphism (rs6918698; -945 G/C) was identified according to the chimeric cycling probe method. The rate of liver fibrosis progression was measured using two liver fibrosis prediction formulas, the Forns index and the FibroIndex. All HCC patients were followed regularly every month. Results The frequency of the -945 C allele was higher among the LC patients than the CH patients. Regarding the rate of liver fibrosis progression over five years, C homozygotes tended to exhibit a faster rate than G carriers, although the difference was not significant. Among the LC patients, the C homozygotes demonstrated lower prothrombin times, higher rates of indocyanine green retention and higher Child-Pugh scores than the G carriers. There were no significant tendencies in the genotype distribution, irrespective of the status of HCC. However, the prognosis of HCC was poorer for the C homozygotes than for the G carriers. Conclusion A CTGF -945 C homozygote status is a significant risk factor for the progression of HCVrelated chronic liver disease, including HCC.

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Association of TIMP-1 and TIMP-2 Gene Polymorphisms with Progression of Liver Fibrosis in Patients with Type C Chronic Liver Disease

Cited by 6 publications

References 30 publications

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

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

Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

Association between Gene Polymorphisms of Connective Tissue Growth Factor and the Progression of Chronic Liver Disease Associated with Hepatitis C

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