PROTECTION AGAINST BRONCHIAL-ASTHMA BY CFTR DELTA-F508 MUTATION - A HETEROZYGOTE ADVANTAGE IN CYSTIC-FIBROSIS

Cystic fibrosis (CF) is a multisystem autosomal recessive disorder cau sed by mutations of the cystic fibrosis transmembrane regulator (CFTR) , a protein that regulates cyclic-AMP-mediated chloride conductance at the apical membrane of secretory epithelia(1). Mutations in the CFTR gene are common in many populations. In North America, 4-5% Of the gen eral population are heterozygous for a CFTR mutation(2). Although ther e are over 400 known CFTR mutations, a single mutation, a deletion of the phenylalanine at position 508 (Delta F508) in exon 10, accounts fo r about 70% of all CF chromosomes worldwide(3). The reasons for the hi gh frequency of the Delta F508 CFTR allele - the selective advantage a ssociated with CF heterozygosity - are unknown(1). Many physiological abnormalities have been observed in CF heterozygotes(4-6), although th e clinical significance of these observations is unknown. Preliminary unpublished data and anecdotal information from CF families suggested that, remarkably, the Delta F508 allele might protect heterozygotes ag ainst bronchial asthma prompted us to further investigate this possibi lity. Here we present evidence that the Delta F508 CF allele protects against asthma in childhood and early adult life.