Ficolin-2 Levels and FCN2 Haplotypes Influence Hepatitis B Infection Outcome in Vietnamese Patients

Abstract

Human Ficolin-2 (L-ficolins) encoded by FCN2 gene is a soluble serum protein that plays an important role in innate immunity and is mainly expressed in the liver. Ficolin-2 serum levels and FCN2 single nucleotide polymorphisms were associated to several infectious diseases. We initially screened the complete FCN2 gene in 48 healthy individuals of Vietnamese ethnicity. We genotyped a Vietnamese cohort comprising of 423 clinically classified hepatitis B virus patients and 303 controls for functional single nucleotide polymorphisms in the promoter region (-986G>A, -602G>A, -4A>G) and in exon 8 (+6424G>T) by real-time PCR and investigated the contribution of FCN2 genotypes and haplotypes to serum Ficolin-2 levels, viral load and liver enzyme levels. Haplotypes differed significantly between patients and controls (P = 0.002) and the haplotype AGGG was found frequently in controls in comparison to patients with hepatitis B virus and hepatocellular carcinoma (P = 0.0002 and P<0.0001) conferring a protective effect. Ficolin-2 levels differed significantly between patients and controls (p<0.0001). Patients with acute hepatitis B had higher serum Ficolin-2 levels compared to other patient groups and controls.The viral load was observed to be significantly distributed among the haplotypes (P = 0.04) and the AAAG haplotype contributed to higher Ficolin-2 levels and to viral load. Four novel single nucleotide polymorphisms in introns (-941G>T, -310G>A, +2363G>A, +4882G>A) and one synonymous mutation in exon 8 (+6485G>T) was observed. Strong linkage was found between the variant -986G>A and -4A>G. The very first study on Vietnamese cohort associates both Ficolin-2 serum levels and FCN2 haplotypes to hepatitis B virus infection and subsequent disease progression.

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

“…Additionally, our study also showed that there are associations between 258S variant and L-ficolin level in the patients. The association between low L-ficolin levels and the 258S variant has also formerly been observed in other settings: healthy Danish individuals [13], Polish children with recurrent infections [12], Gabonese malaria patients (but not controls) [16], Vietnamese HBV-infected patients and controls [15].…”

“…No significant difference of haplotype distribution was observed between different groups, nevertheless, − 4 A/G heterozygotes was observed to associate with the disease when compared cardiac patients to the controls as well as cardiac to the indeterminate patients. In addition, the AGG promoter haplotype, whose presence is obligatory in − 4 A/G heterozygotes, was also associated with protection against HBV infection in Vietnamese [15], but with susceptibility to schistosomiasis in Nigeria [17]. Our group found the AGA haplotype to be associated with protection against clinical leprosy and rheumatic fever [14], [18], whereas others found it associated with susceptibility to cutaneous leishmaniasis [28].…”

“…Of which individuals with the less severe B form had higher L-ficolin levels than the C and D forms. Interestingly, median L-ficolin levels are higher in acute than in chronic hepatitis B conditions [15]. They are also higher in acute malaria, compared with the levels after treatment [16], but lower in Schistosoma haematobium -infected individuals from Nigeria, compared to controls [17].…”

Early Increased Ficolin‐2 Concentrations are Associated with Severity of Liver Inflammation and Efficacy of anti‐Viral Therapy in Chronic Hepatitis C Patients

“…MBL has been described as an acute-phase protein, and the association of MBL with viral hepatitis has been investigated by many groups [24]. However, little was reported about the function of ficolins in viral hepatitis [25,26].…”

Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection

“…The H-ficolin (H-FCN, FCN-3) gene (FCN3) is a pseudogene in the murine lineage. Accumulating data indicate that each ficolin recognizes an overlapping spectrum of microorganisms (5,6,19,20), and that the deficiency and/or low level of human ficolins has been associated with specific infectious diseases (21)(22)(23).…”