Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients.
OBJECTIVE
Mannose-binding lectin, a key factor of the innate immune system, has genetic polymorphism, and individuals who carry certain genotypes of mannose-binding lectin are known to be more prone to severe or prolonged infectious diseases. We aimed to find any relevance of mannose-binding lectin polymorphism to hepatitis C virus infection.


METHODS
We determined the mannose-binding lectin genotypes by sequence specific priming-polymerase chain reaction in 159 hepatitis C virus-infected chronic hepatitis patients and 218 healthy controls in Japan by looking at 4 polymorphic loci: 2 (H/L and X/Y) within the promoter region and 2 (P/Q and A/B) within exon-1 of the mannose-binding lectin gene.


RESULTS
A group of mannose-binding lectin genotypes designated "XB-type" (containing LXPA or LYPB haplotype at least heterozygously) was less frequently found in interferon-responsive patients (38.5%) than in interferon-resistant patients (60.7%, p=0.008) and controls (57.3%, p=0.014). Individuals with the "XB-type" had lower serum concentrations of mannose-binding lectin, compared to those with "YA-type", which is defined by homozygous carriage of both Y and A alleles: 0.63+/-0.61 vs 2.06+/-1.17 mg/l, p<0.001.


CONCLUSIONS
Our results suggest that the mannose-binding lectin-related innate immune system plays an important role in elimination of hepatitis C virus during interferon therapy. Determining mannose-binding lectin genotypes may help in selecting the hepatitis C virus-infected patients to be treated with interferon.
Matsushita
M
M
Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan.
Hijikata
M
M
Matsushita
M
M
Ohta
Y
Y
Mishiro
S
S
D000998:Antiviral Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D037222:Collectins; D004351:Drug Resistance / Q000235:genetics*; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007564:Japan; D011110:Polymorphism, Genetic
D000998:Antiviral Agents; D002352:Carrier Proteins; D037222:Collectins; D007372:Interferons