Association of pulmonary surfactant protein A (SP-A) gene and respiratory distress syndrome: Interaction with SP-B

Deficiency of the lipoprotein complex, surfactant, can lead to respiratory distress syndrome (RDS) in the prematurely born infant. The surfactant proteins (SP) play important roles in the function of surfactant. Previously, we have characterized four allelic variants of the SP-A1 gene (6A, 6A(2), 6A(3), and 6A(4)) and five allelic variants of the SP-A2 gene (1A, 1A(0), 1A(1), 1A(2), and 1A(3)). We hypothesized that specific SP-A alleles/genotypes are associated with increased risk of RDS. Because race, gestational age (GA), and sex are risk factors for RDS, we first studied the distribution and frequencies of SP-A alleles/genotypes while adjusting for these factors as confounders or effect modifiers in control (n = 86 white and 12 black subjects) and RDS (n = 106 white and 37 black subjects) populations with GAs ranging from 24 wk to term. Although the odds ratios of several alleles and genotypes were in the opposite directions for black and white subjects, the homogeneity of odds ratio reached statistical significance only in the case of 6A(3)/6A(3). Although differences were observed in subgroups with different GAs (less than or equal to 28 and > 28 wk) of the RDS white population, definitive conclusions cannot be made regarding the effect of modification by GA. No differences were observed as a function of sex. Second, we compared the frequencies of SP-A genotypes and alleles between control (n = 83) and RDS (n = 82) patients in the > 28-wk white population. Differences between the two groups were observed for the 1A(0) allele and 1A(0) genotypes. Moreover, a significant synergistic positive association was observed between 1A(0) allele + SP-B polymorphic variant and RDS. We conclude that 1) the genetic analyses of RDS and SP-A locus should be performed separately for black and white populations and 2) SP-A alleles/genotypes and SP-B variant may contribute to the etiology of RDS and/or may serve as markers for disease subgroups.