The impact of cyclooxygenase-2 gene polymorphism 899G/C and certain indices on hepatitis C related liver fibrosis

Abstract

The link between cyclooxygenase-2 (COX-2) gene polymorphisms and liver diseases has been widely reported. Early and precise estimation and staging of hepatic fibrosis are crucial for prognosis and treatment decisions in those patients. We aimed in this study to clarify role of -899G/C polymorphism of COX-2 gene, alteration of CA 19-9 and CA 125 levels, and plasma protein pattern in staging of liver fibrosis comparing them to METAVIR stages of liver fibrosis. We recruited 103 patients with post-hepatitis C liver fibrosis and 42 healthy controls. COX-2 gene polymorphism was detected by PCR- TaqMan probes, while CA19-9, CA125 levels were estimated using quantitative ELISA. Plasma proteins were detected by the capillary electrophoresis method. The results revealed that the frequency of COX-2 -899G/C genotypes GG, GC, and CC were 68.0%, 28.2% and 3.9% in the fibrotic group; 97.06%, 2.4%, and 0.0% in healthy control group respectively. The percent of COX-2 expression for the fibrotic group and the healthy group were 32% and 2.3% respectively. COX-2 expression scores on mild- vs. sever-fibrosis stages (METAVIR stages 1, 2 vs. stages 3,4) were 18.2 %and 81.8% respectively (OR=48.00, 95%CI). The serum level of tested tumor markers were significantly higher in fibrotic patients than in control group (69.40 ±51.82, 13.41 ± 6.49 respectively for CA 19.9 and 59.16 ± 47.23, 10.90 ± 8.36 for CA 125) and in GC/CC genotypes than GG one (116.96 ± 55.00, 33.64 ± 28.39 respectively for CA 19.9 and 101.62 ± 51.29, 27.89 ± 25.51 respectively for CA 125). In conclusion, COX-2 -899 C allele carriers are more vulnerable to develop hepatitis C- related hepatic fibrosis. The combined estimation of CA 19-9 and CA 125 levels are useful for identifying and staging patients with liver fibrosis.

Keywords: COX-2 gene polymorphisms, CA 19-9, CA 125, protein electrophoresis, liver fibrosis