SP-A and SP-B polymorphisms are found at a higher frequency in certain groups of patients with respiratory distress syndrome (RDS), and SP-B mutations are linked to the pathogenesis of congenital alveolar proteinosis (CAP).
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.
Among the infants born before 32 weeks of gestation and having the SP-B genotype Thr/Thr, the SP-A1 allele 6A(2) was over-represented in RDS group compared with controls (P = 0.001, OR = 4.7, CI 1.8-12.2).
The present family study provides strong support for a direct or indirect role of the SP-A alleles as genetic predisposers to RDS in premature infants.
Allelic variations of the SP-A and SP-B genes have been shown to be important genetic determinants in individual susceptibility to RDS, which is a good general model for a multifactorial pulmonary disease resulting from complex interactions between several environmental and genetic factors.
The SP-A 6A2 allele in the SP-B Thr131 background predisposed the smallest singleton infants to RDS, whereas near-term multiples were protected from RDS.
The difference in RDS concordance rates between the monozygotic (MZ) and dizygotic (DZ) twin pairs as evidence of a genetic influence was evaluated, and the SP-A and SP-B genes were investigated for potential associations with the susceptibility to RDS.
The main SP-A1 allele 6A2 (P = 0.030), genotype 6A2/6A2 (P = 0.0042) and haplotype 6A2-1A(0) (P = 0.016) were over-represented in healthy premature twin infants compared to RDS twins.
Single-nucleotide polymorphisms (SNPs) in SP-A1 and SP-A2, genes encoding SP-A, have been associated with susceptibility to respiratory distress syndrome, COPD, and pulmonary infections.
To determine whether haplotypes of SP-A and SP-D are transmitted disproportionately from parents to offspring with RDS, we hypothesized that previously unstudied genetic haplotypes of these SP genes are associated with the development of RDS.
Overall, the SP-A1 6A4 or/and SP-A2 1A5 haplotype was present in 20 newborns with RDS (35.7%), resulting in a 4.2-fold (1.60-11.0) higher probability of RDS in carriers.