CFTR gene mutations in sarcoidosis

Abstract

Sarcoidosis is a complex disease of multiorgan granulomatous inflammation. Genetic susceptibility is involved in the pathogenesis of the disorder. Two successive studies from Italy have shown a high frequency of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suffering from sarcoidosis. We have genotyped a panel of 63 families with two or more affected siblings for the CFTR gene mutation R75Q, which was found to be present in three of 26 cases of the Italian study. Although R75Q was present in seven families, it was neither associated with the sarcoidosis phenotype in the German population (P=0.5), nor was it linked to sarcoidosis (P=0.54). In addition, a screening for 34 functional CFTR mutations was performed in a subset of 54 patients from 25 families. These patients were known to be concordant for at least one parental copy of the CFTR gene. With the exception of the mayor CF mutation ‡F508, which was present in three patients and absent in one patient from two families, we did not find any other CF mutation in these 54 patients. Our results do not support the hypothesis that CFTR mutations have a major influence on the pathogenesis of sarcoidosis.