Genetics of the hydrophilic surfactant proteins A and D.
The use of candidate genes has increased the ability to identify genetic factors involved in diseases with complex and multifactorial etiology. 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 particularly good candidates to study factors contributing to pulmonary disease etiopathogenesis. Moreover, SP-A also plays a role in the surface tension lowering abilities of pulmonary surfactant, which is essential for normal lung function. Although genetic variability at the SP-D locus may exist among humans, allelic variants have not yet been characterized. On the other hand, the human SP-A genes (SP-A1 and SP-A2) are characterized by genetically dependent splice variants at the 5' untranslated region and allelic variants. The polymorphisms that give rise to SP-A1 and SP-A2 alleles are contained within coding regions, potentially having an effect on protein function. There appears to be a correlation between SP-A genotype and SP-A mRNA content. Furthermore, one SP-A2 allele (1A0) 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 interacting with other surfactant components, may play a role (e.g. be a susceptibility factor) in the development of respiratory disease.
Floros
J
J
Department of Cellular and Molecular Physiology H166, Pennsylvania State University College of Medicine, P.O. Box 850, 500 University Dr., Hershey, PA 17033, USA. jxf19@psu.edu
Hoover
R R
RR
D017398:Alternative Splicing; D002879:Chromosomes, Human, Pair 10; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008171:Lung Diseases / Q000209:etiology*; D020412:Multifactorial Inheritance; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics
D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human