DINUCLEOTIDE REPEATS IN THE HUMAN SURFACTANT PROTEIN-B GENE AND RESPIRATORY-DISTRESS SYNDROME

Pulmonary surfactant, a lipoprotein complex, is essential for normal l ung function, and deficiency of surfactant can result in respiratory-d istress syndrome (RDS) in the prematurely born infant. Some studies ha ve pointed towards a genetic contribution to the aetiology of RDS. Bec ause the surfactant protein B (SP-B) is important for optimal surfacta nt function and because it is involved in the pathogenesis of pulmonar y disease, we investigated the genetic variability of the SP-B gene in individuals with and without RDS. We identified a 2.5 kb BamHI polymo rphism and studied its location, nature and frequency. We localized th is polymorphism in the first half of intron 4 and found that it is der ived by gain or loss in the number of copies of a motif that consists of two elements, a 20 bp conserved sequence and a variable number of C A dinucleotides. Variability in the number of motifs resulting from ei ther deletion (in 55.3% of the cases with the variation) or insertion (44.7%) of motifs was observed in genomic DNAs from unrelated individu als. Analysis of 219 genomic DNAs from infants with (n = 82) and witho ut (n = 137) RDS showed that this insertion/deletion appears with sign ificantly higher frequency in the RDS population (29.3 as against 16.8 %, P < 0.05).