The mannose binding lectin gene influences the severity of chronic liver disease in cystic fibrosis

Chronic liver disease is a major complication of cystic fibrosis. Its incid ence and severity show marked heterogeneity, even among the homogeneous gro up of homozygous Delta F508 patients, suggesting that environmental or gene tic factors other than the deletion Delta F508 may influence the developmen t of cystic fibrosis related liver disease. We investigated whether the all elic variants of mannose binding lectin, an important protein of the immune system, could be associated with the presence of cirrhosis in a population of 216 homogeneous homozygous Delta F508 patients. Analysis of the data sh ows that the presence of cirrhosis in cystic fibrosis patients is significa ntly associated with a mutated mannose binding lectin genotype (homozygous or compound heterozygous for mannose binding lectin variants). The modulati ng role of mannose binding lectin in the occurrence of cirrhosis in cystic fibrosis could be explained by the fact that hepatotoxic damage from viruse s or bacteria might be increased by the immunodeficiency associated with ma nnose binding lectin variants and might facilitate the degradation of liver status. These data highlight the crucial role of mannose binding lectin in the clinical outcome of cystic fibrosis, as it has recently been shown tha t the mannose binding lectin gene is a modulating gene of the respiratory i nvolvement in cystic fibrosis patients.