MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response

Abstract

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannosebinding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.

The Complement System and C1q in Chronic Hepatitis C Virus Infection and Mixed Cryoglobulinemia

“…In vitro studies showed that mannan-binding lectin (MBL) bound to the HCV E2 ectodomain and E1/E2 heterodimers through its lectin domain, as well as activate complement through MBL-associated serine protease 2 ( 49 ). Ficolin-2, a known lectin pathway activator was found to inhibit attachment of HCV envelope E1 and E2 N-glycans to their low-density lipoprotein (LDL) and scavenger B1 receptors ( 50 ), with elevated blood levels of L-ficolin or MBL being found in the serum of some patients, possibly correlating with MBL2 genetic variants and response to IFNα ( 51 ).…”

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

“…Interestingly, Kilpatrick showed a slight relationship between the high level of MBL and chronicity of HCV [37]. However, Zupin [39] were reported the association of the SNPs with SVR instead of susceptibility to HCV or viral clearance. The level of all other PRRs should be encountered when studying the immune system.…”

HBV Viral Load and Liver Enzyme Levels May Be Associated with the WildMBL2AA Genotype

“…Recently, it was reported that the presence of mutant alleles in the promoter region (−221 C>G) of the MBL2 gene could protect against the more severe forms of the liver injury (cirrhosis and HCC) [21], and a better liver function was shown as associated with high MBL serum levels [22]. Furthermore, Zupin et al [23] reported that MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 ∗ O allele, OO genotype, and HYO haplotype, all correlated with low or deficient MBL expression, were associated with sustained virological response (SVR).…”