Human Molecular Genetics, 2000, Vol. 9, No. 18 2751-2760
© 2000 Oxford University Press
Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome
1Department of Paediatrics and Biocenter Oulu, University of Oulu, PO Box 5000, FIN-90014 Oulu, Finland and 2Laboratory of Developmental Immunology, Massachussetts General Hospital, Boston, MA, USA
Prematurity is the most important risk factor predisposing to neonatal respiratory distress syndrome (RDS). Genetic factors are likely to contribute to the risk of this complex disease. The present study was designed to investigate whether the surfactant protein B (SP-B) gene or interaction between the SP-A and SP-B genes has a role in the genetic susceptibility to RDS. The genotype analyses were performed on 684 prematurely born neonates, of whom 184 developed RDS. Of the two SP-B polymorphisms genotyped, the Ile131Thr variation affects a putative N-terminal N-linked glycosylation site of proSP-B and the length variation of intron 4 has previously been suggested to associate with RDS. Neither of the two SP-B polymorphisms associated directly with RDS or with prematurity. Instead, our data show that the previously identified association between SP-A alleles and RDS was dependent on the SP-B Ile131Thr genotype. On the basis of 
2 and logistic regression analyses, the SP-A allele, haplotype and genotype distributions differed significantly between the RDS infants and controls only when the SP-B genotype was Thr/Thr. Among the infants born before 32 weeks of gestation and having the SP-B genotype Thr/Thr, the SP-A1 allele 6A2 was over-represented in RDS group compared with controls (P = 0.001, OR = 4.7, CI 1.8–12.2). In the same comparison, the SP-A1 allele 6A3 was under-represented in RDS (P = 0.001, OR = 0.2, CI 0.1–0.6). We propose that the SP-B Ile131Thr polymorphism is a determinant for certain SP-A alleles as factors causing genetic susceptibility to RDS (6A2, 1A0) or protection against it (6A3, 1A2).
+ To whom correspondence should be addressed. Tel: +358 8 315 5100; Fax: +358 8 315 5559; Email: mhallman@cc.oulu.fi
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