Liver expression in cystic fibrosis could be modulated by genetic factors different from the cystic fibrosis transmembrane regulator genotype

During a multicentric study conducted in Southern Italy, we studied five se ts of cystic fibrosis siblings bearing a strongly discordant liver phenotyp e, three with genotype Delta F508/R553X, one with genotype Delta F508/unkno wn, and one with genotype unknown/unknown. The siblings of each set were ra ised in the same family environment, and there were no interpair difference s in nutritional state or in therapy compliance. All siblings had pancreati c insufficiency and moderate respiratory expression, One sibling of each of the five sets was free of liver involvement, and the other had severe live r expression. Other causes of liver disease (viral, metabolic, and genetic other than cystic fibrosis) were ruled out. Therefore, environmental factor s, nutritional state, and therapy compliance are not involved in the liver expression of cystic fibrosis in the five unrelated sibships, This suggests that modifier genes, inherited independently of the cystic fibrosis transm embrane regulator gene, could modulate the liver expression in cystic fibro sis patients. (C) 2001 Wiley-Liss, Inc.