A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A2 and 1A0 and of 1A0/6A2 haplotype in RDS was increased, whereas transmission of alleles 1A5 and 6A4 and of haplotype 1A5/6A4 was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A0 and 6A2 or 1A0, were increased, respectively, but the frequency of specific 6A3 genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A3 genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A0, 6A2, 1A0/6A2) or protective (1A5, 6A4, 1A5/6A4) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.
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