Surfactant Protein A and B Genetic Variants in Respiratory Distress Syndrome in Singletons and Twins

Riitta Marttila, Ritva Haataja, Susan Guttentag, Mikko Hallman
2003 American Journal of Respiratory and Critical Care Medicine  
Interactive genetic and environmental factors may influence the differentiation of surfactant and the risk of respiratory distress syndrome (RDS). DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population. Distributions of the SP-A and SP-B gene variants between RDS and no-RDS infants were determined alone and in
more » ... tion. SP-A1 allele 6A 2 (p ϭ 0.009) and the homozygous genotype 6A 2 /6A 2 (p ϭ 0.003) were overrepresented in RDS of singletons when the SP-B exon 4 genotype was Thr/Thr, and underrepresented in RDS of multiples when the SP-B genotype was Ile/Thr (p ϭ 0.012 for 6A 2 and p ϭ 0.03 for 6A 2 /6A 2 ) or Thr/Thr (p ϭ 0.12 for 6A 2 and p ϭ 0.018 for 6A 2 /6A 2 , respectively). The SP-A 6A 2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS. There was a continuous association between fetal mass and risk of RDS, defined by the SP-A and SP-B variants. Labeled lung explants with the Thr/Thr genotype showed proSP-B amino-terminal glycosylation, which was absent in Ile/Ile samples. Genetic and environmental variation may influence intracellular processing of surfactant complex and the susceptibility to RDS. Keywords: fetal mass; interaction of genes and environment; surfactant protein polymorphism Respiratory distress syndrome (RDS) in premature infant remains the major life-threatening neonatal disease affecting 1 to 2% of newborn infants despite antenatal steroid and surfactant treatments (1, 2). RDS is principally associated with developmental deficiency in synthesis, intracellular processing, and secretion of pulmonary surfactant, required to reduce surface tension at the air-liquid interface of the distal conducting airways and alveoli. Pulmonary surfactant consists of lipids and surfactant-specific proteins (SPs); these components each exhibit developmental regulation. Some SP-B and -C mRNAs are expressed early in the second trimester, and SP-A early in the third trimester, as studied in explants from the human lung (3). It is therefore understandable that factors influencing the expression of any or all of these components, particularly the degree of prematurity but also sex, ethnicity, inflammation, and genetic factors, influence the disease risk (4-9). The polymorphisms of the SP-A1, SP-A2, and SP-B genes have been studied for associations with RDS (9-14). On the basis of our earlier observations in different sets of Finnish neonates, the allelic associations between SP-A or SP-B genes and RDS
doi:10.1164/rccm.200304-524oc pmid:12947025 fatcat:ll7hpmoavrgutmi6suwlydfa2q