GENETICS OF THE HYDROPHILIC SURFACTANT PROTEIN-A AND PROTEIN-D

The use of candidate genes has increased the ability to identify genet ic factors involved in diseases with complex and multifactorial etiolo gy. The surfactant proteins (SP) A and D are involved in host defense and inflammatory processes of the lung, which are often components of pulmonary disease. Therefore, the SP-A and SP-D genes make particularl y good candidates to study factors contributing to pulmonary disease e tiopathogenesis. Moreover, SP-A also plays a role in the surface tensi on lowering abilities of pulmonary surfactant, which is essential for normal lung function. Although genetic variability at the SP-D locus m ay exist among humans, allelic variants have not yet been characterize d. On the other hand, the human SP-A genes (SP-A1 and SP-A2) are chara cterized by genetically dependent splice variants at the 5' untranslat ed region and allelic variants. The polymorphisms that give rise to SP -AI and SP-A2 alleles are contained within coding regions, potentially having an effect on protein function. There appears to be a correlati on between SP-A genotype and SP-A mRNA content. Furthermore, one SP-A2 allele (1A(0)) shown to associate with low SP-A mRNA levels is found with higher frequency in a subgroup with respiratory distress syndrome . The evidence gathered thus far indicates that SP-A, possibly by inte racting with other surfactant components, may play a role (e.g. be a s usceptibility factor) in the development of respiratory disease. (C) 1 998 Elsevier Science B.V. All rights reserved.