Surfactant proteins and genetic predisposition to respiratory distress syndrome.
Respiratory distress syndrome (RDS) is caused by surfactant deficiency at birth. The risk of RDS decreases from the gestational age of 24 weeks to full-term. Genetic and acquired factors additionally influence the risk of RDS. Surfactant deficiency in RDS is mainly caused by immaturity and a lack of differentiation of the alveolar epithelial cells involved in surfactant synthesis and secretion. A network of hormones and growth factors regulate perinatal development. Host-related factors, including the levels of expression of surfactant proteins (SP), modulate the responsiveness of growth factors. SP-A has roles in surface activity and regulatory roles particularly in innate immunity; SP-B is essential for the processing of surfactant and for the surface activity; SP-C has roles in surfactant metabolism and function; the regulatory roles of SP-D mainly pertain to innate immunity. The genetic variation of SP-A and SP-B genes and the risk of RDS have been studied. Both SP-A and SP-B associate with susceptibility to RDS. The association between the SP-A allele and genotypes and the risk of RDS is dependent on the SP-B genotype and significantly influenced by the degree of prematurity, antenatal glucocorticoid therapy, multiple birth, and birth order. The alleles/genotypes of SP-A, SP-C, or SP-D also associate with several other inflammatory lung and airway diseases. Rare mutations in SP-B or SP-C cause serious, often fatal lung diseases. Genetic and post-genomic research is likely to eventually result in new diagnostic applications and specific therapies for the prevention of respiratory failure and inflammatory lung diseases.
Hallman
Mikko
M
Department of Pediatrics and Biocenter Oulu, University of Oulu, Finland. Mikko.Hallman@oulu.fi
Haataja
Ritva
R
Marttila
Riitta
R
D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D011110:Polymorphism, Genetic; D037661:Pulmonary Surfactant-Associated Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics* / Q000378:metabolism
D037661:Pulmonary Surfactant-Associated Proteins