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

Abstract

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.

Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities

“…Functional single nucleotide polymorphisms (SNPs, rs6918698) implicated CCN2 as a major actor in severe HF in schistosome-infected Chinese, Sudanese, and Brazilian subjects [ 64 ]. Another study further confirmed that one CTGF gene polymorphism (rs6918698; −945 G/C) is a significant risk factor for the progression of hepatitis C-related chronic liver diseases [ 65 ].…”

Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity

“…This SNP was used in our study but was not associated with longevity. The CC minor allele homozygote of CTGF variant rs6918698 is located in the promoter at -945 and is a significant risk factor for the progression of hepatitis C virus-related chronic liver disease, including hepatocellular carcinoma (36). The GG major allele homozygote of CTGF variant rs6918698 was associated with an older age of onset of Crohn's disease (37).…”