Association of mannose-binding lectin gene haplotype LXPA and LYPB with interferon-resistant hepatitis C virus infection in Japanese patients

Background/Aims: 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/O 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.