title: 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.
authors.affiliation: Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. tong.van-hoang@uni-tuebingen.de
authors.forename: Tong V
authors.initials: TV
authors.lastname: Hoang
authors.forename: Nguyen L
authors.initials: NL
authors.lastname: Toan
authors.forename: Le H
authors.initials: le H
authors.lastname: Song
authors.forename: Eman Abou
authors.initials: EA
authors.lastname: Ouf
authors.forename: C-Thomas
authors.initials: CT
authors.lastname: Bock
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: T P
authors.initials: TP
authors.lastname: Velavan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006509:Hepatitis B / Q000097:blood / Q000235:genetics* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014744:Vietnam; D019562:Viral Load / Q000235:genetics; D055815:Young Adult; D000097604:Ficolins
chemical_list: D037102:Lectins; D000097604:Ficolins