Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection

Mannose‐binding lectin (MBL) plays an important role in immune defense. We examined the MBL gene mutations and MBL levels in Chinese hepatitis B and hepatitis C patients with and without symptomatic cirrhosis. We recruited 190 hepatitis B and C patients, and 117 normal Chinese as controls. Serum MBL levels were measured by enzyme‐linked immunosorbent assay. MBL gene mutation at codons 52, 54, and 57 was detected by polymerase chain reaction (PCR) assay. In asymptomatic hepatitis B and C patients, there was no increase in codons 52, 54, and 57 mutation, but the MBL levels were significantly lower than those in the controls. Codon 54 mutation rate was increased to 44.4% (P = .007) in symptomatic hepatitis B cirrhosis and 64.3% (P = .0026) in patients with spontaneous bacterial peritonitis (SBP). There was no increase in codon 54 mutation rate in hepatitis B–related hepatocellular carcinoma (HCC). In chronic hepatitis B infection, the odds ratio for an individual with codon 54 mutation to develop cirrhosis was 1.84 (95% CI: 1.21‐2.81) and to develop SBP was 4.58 (95% CI: 1.73‐12.16). Chronic hepatitis B and hepatitis C infection lowered the MBL levels, probably by suppressing MBL production. Codon 54 mutation of MBL was associated with progression of disease in chronic hepatitis B infection

[1]  G. Foster,et al.  Mutation of gene for mannose-binding protein associated with chronic hepatitis B viral infection , 1996, The Lancet.

[2]  A. Spurdle,et al.  Mutations in the Human Mannose-Binding Protein Gene: Frequencies in Several Population Groups , 1996, European journal of human genetics : EJHG.

[3]  S. Thiel,et al.  Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis. , 2008, Liver.

[4]  S. Thiel,et al.  Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. , 1995, Journal of immunology.

[5]  L. Bland,et al.  Transmission of HIV in dialysis centre , 1995, The Lancet.

[6]  M. Turner,et al.  Mannose binding protein gene mutations associated with unusual and severe infections in adults , 1995, The Lancet.

[7]  J. Summerfield,et al.  Mannose binding protein is involved in first-line host defence: evidence from transgenic mice. , 1995, Immunology.

[8]  Robert B Sim,et al.  Localization of the receptor-binding site in the collectin family of proteins. , 1993, The Biochemical journal.

[9]  A. Hill,et al.  High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene , 1992 .

[10]  T. Fujita,et al.  Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease , 1992, The Journal of experimental medicine.

[11]  R. Levinsky,et al.  Molecular basis of opsonic defect in immunodeficient children , 1991, The Lancet.

[12]  M. Okada,et al.  The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. , 1990, The Journal of biological chemistry.

[13]  M. Turner,et al.  The level of mannan‐binding protein regulates the binding of complement‐derived opsonins to mannan and zymosan at low serum concentrations , 1990, Clinical and experimental immunology.

[14]  S. Thiel,et al.  ASSOCIATION OF LOW LEVELS OF MANNAN-BINDING PROTEIN WITH A COMMON DEFECT OF OPSONISATION , 1989, The Lancet.

[15]  M. Taylor,et al.  Structure and evolutionary origin of the gene encoding a human serum mannose-binding protein. , 1989, The Biochemical journal.

[16]  K. Joiner,et al.  The human mannose-binding protein functions as an opsonin , 1989, The Journal of experimental medicine.

[17]  Ching-lung Lai,et al.  PLACEBO-CONTROLLED TRIAL OF RECOMBINANT α2-INTERFERON IN CHINESE HBsAg-CARRIER CHILDREN , 1987, The Lancet.

[18]  B. Winchester,et al.  Isolation of mannose-binding proteins from human and rat liver. , 1983, The Biochemical journal.

[19]  R. Williams,et al.  Impaired opsonization by serum from patients with chronic liver disease. , 1983, Clinical and experimental immunology.