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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.

SUBMITTER: Hoang TV

PROVIDER: S-EPMC3222672 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients.

Hoang Tong V TV Toan Nguyen L NL Song Le H le H Ouf Eman Abou EA Bock C-Thomas CT Kremsner Peter G PG Kun Jürgen F J JF Velavan T P TP

PloS one 20111122 11

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 function ...[more]

PMID: 22140517

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Project description:BackgroundL-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.MethodsWe investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (-986 G>A, -602 G>A, and -4 A>G in the promoter and A258S in exon 8) in 243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified) and 305 controls (135 for A258S).ResultsPatients presented lower L-ficolin plasma levels than controls (p<0.0001). Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039). Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034). We found less -4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33-0.94], P = 0.034). Heterozygote -4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5-56.8], P = 0.0001) and in indeterminate patients (OR = 3.2 [95% CI = 1.1-9.4], P = 0.037). We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1-4.5], P = 0.037). Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms.ConclusionThe very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism should be further evaluated in other settings.

Project description:The complement system is a key component of the innate immune system, participating in the surveillance against infectious agents. Once activated by one of the three different pathways, complement mediates cell lysis, opsonization, signalizes pathogens for phagocytosis and induces the adaptive immune response. The lectin pathway is constituted by several soluble and membrane bound proteins, called pattern recognition molecules (PRM), including mannose binding lectin (MBL), Ficolins-1, -2, and -3, and Collectin 11. These PRMs act on complement activation as recognition molecules of pathogen-associated molecular patterns (PAMPs) such as N-acetylated, found in glycoproteins of viral envelopes. In this study, Ficolin-1 and Ficolin-3 plasma levels were evaluated in 178 HIV patients (93 HIV; 85 HIV/HCV) and 85 controls from southern Brazil. Demographic and clinical-laboratory findings were obtained during medical interview and from medical records. All parameters were assessed by logistic regression, adjusted for age, ancestry, and sex. Significantly lower levels of Ficolin-1 were observed in HIV/HCV coinfected when compared to HIV patients (p = 0.005, median = 516 vs. 667 ng/ul, respectively) and to controls (p < 0.0001, 1186 ng/ul). Ficolin-1 levels were lower in males than in females among HIV patients (p = 0.03) and controls (p = 0.0003), but no association of Ficolin-1 levels with AIDS was observed. On the other hand, Ficolin-3 levels were significantly lower in controls when compared to HIV (p < 0.0001, medians 18,240 vs. 44,030 ng/ml, respectively) and HIV/HCV coinfected (p < 0.0001, 40,351 ng/ml) patients. There was no correlation between Ficolin-1 and Ficolin-3 levels and age, HIV viral load or opportunistic infections. However, Ficolin-3 showed a positive correlation with T CD4 cell counts in HIV monoinfected patients (p = 0.007). We provide here the first assessment of Ficolin-1 and-3 levels in HIV and HIV/HCV coinfected patients, which indicates a distinct role for these pattern recognition molecules in both viral infections.

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Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients.

Publications

Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients.

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