Mutation of gene of mannose-binding protein associated with chronic hepatitis B viral infection.
BACKGROUND
Persistent with hepatitis B virus (HBV) affects 350 million people worldwide, and 20-40% of infected patients die of cirrhosis and liver cancer. Little is known about the host factors that determine the variable natural history. Studies have focused on the role of acquired rather than innate immunity. We have investigated the prevalence of mutations in the gene for mannose-binding protein (MBP), which have been associated with susceptibility to bacterial and fungal infections.


METHODS
Mutations in the MBP gene were sought by sequence-specific oligonucleotide hybridisation, site-directed sequencing in Caucasian and Asian patients with HBV infection, and in HBsAg-negative controls.


RESULTS
A mutation in codon 52 of the MBP gene was present in two (11%) of 19 Caucasian patients with acute hepatitis B and nine (27%) of 33 Caucasian patients with chronic hepatitis B, compared with four (4%) of 98 Caucasian controls (p = 0.0004). By contrast the prevalence of the mutation was similar in Asian patients with chronic hepatitis B and in Asian controls (one [5%] of 20 vs two [2%] of 117). Mutations in codon 54 and codon 57 were found in similar proportions of patients and controls.


CONCLUSIONS
These findings show in Caucasian, but not Asian, patients an association of the codon 52 mutation of the MBP gene with persistent HBV infection. They suggest an important role for this gene, or a gene in linkage disequilibrium with MBP, in determining outcome after HBV infection in adult but not neonatal life.
Thomas
H C
HC
Department of Medicine, Imperial College School of Medicine, St Mary's Hospital, London, UK.
Foster
G R
GR
Sumiya
M
M
McIntosh
D
D
Jack
D L
DL
Turner
M W
MW
Summerfield
J A
JA
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics*; D000328:Adult; D000483:Alleles; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D002908:Chronic Disease; D003062:Codon; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics*; D006801:Humans; D008297:Male; D008358:Mannose; D037241:Mannose-Binding Lectins; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D044465:White People
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D003062:Codon; D037241:Mannose-Binding Lectins; D008358:Mannose