Mannan-binding lectinMBL2gene polymorphism in chronic hepatitis C: association with the severity of liver fibrosis and response to interferon therapy

Abstract

SummaryHepatitis C virus (HCV) is a major cause of hepatic disease and of liver transplantation worldwide. Mannan-binding lectin (MBL), encoded by the MBL2 gene, can have an important role as an opsonin and complement activating molecule in HCV persistence and liver injury. We assessed the MBL2 polymorphism in 102 Euro-Brazilian patients with moderate and severe chronic hepatitis C, paired for gender and age with 102 HCV seronegative healthy individuals. Six common single nucleotide polymorphisms in the MBL2 gene, three in the promoter (H/L, X/Y and P/Q) and three in exon 1 (A, the wild-type, and B, C or D also known as O) were evaluated using real-time polymerase chain reaction with fluorescent hybridization probes. The concentration of MBL in plasma was measured by enzyme-linked immunosorbent assay. The frequency of the YA/YO genotype was significantly higher in the HCV patients compared with the controls (P = 0·022). On the other hand, the genotypes associated with low levels of MBL (XA/XA, XA/YO and YO/YO) were decreased significantly in the patients with severe fibrosis (stage F4), when compared with the patients with moderate fibrosis (stage F2) (P = 0·04) and to the control group (P = 0·011). Furthermore, MBL2 genotypes containing X or O mutations were found to be associated with non-responsiveness to pginterferon and ribavirin treatment (P = 0·023). MBL2 polymorphisms may therefore be associated not only with the development of chronic hepatitis C, but also with its clinical evolution and response to treatment.

Effects of mannose-binding lectin and mannose-binding lectin polymorphisms on treatment response in patients with chronic hepatitis C

“…Furthermore, MBL levels were found to be higher in patients responding to PEG-IFN treatment than in nonresponders. MBL2 genotypes, including X or O mutations, were found to be associated with treatment failure, and MBL2 genotypes were reported as potentially beneficial in estimating treatment response (21). In the present study, lower MBL levels were detected as the degree of fibrosis increased; however, no significant relationship was found between fibrosis and MBL mutations as in the Pedroso study.…”

“…On the other hand, no difference was found between CHC patients and controls in terms of MBL2 haplotypes and MBL levels in a study conducted by Pedroso et al (21). Mutations leading to lower MBL levels were fewer in patients with advanced fibrosis than in patients with moderate fibrosis; however, no relationship was found between the HCV genotypes and the degree of fibrosis or the MBL2 genotypes.…”

“…A limited number of studies have examined the role of MBL in HCV pathogenesis (4,5,(17)(18)(19)(20)(21). In the studies conducted in Japan, relationships were found between the codon 54 mutation and low MBL levels, disease progression, and treatment response.…”

Evaluation of the cytokine mannose-binding lectin as a mediator of periportal fibrosis progression in patients with schistosomiasis

“…Thus, the present fi nding suggesting high serum MBL levels play an important role in the severity of PPF corroborates other studies reporting similar fi ndings (5) (12) . Therefore, further larger studies analyzing the association between MBL expression and disease outcomes are required to corroborate the present fi ndings and confi rm the profi brotic activity of MBL.…”

“…Pedroso et al (12) compared 102 Euro-Brazilian patients with moderate and severe chronic hepatitis C with sex-and age-matched HCV-seronegative healthy controls and found overall circulating levels of MBL did not differ significantly between groups. However, it is important to note that the exclusion of patients with no or little fi brosis from that study may have weakened the association between disease progression and MBL concentration.…”