Frequency of human SP-A1 and SP-A2 genotypes and alleles in RDS: Impact of confounding factors. 613

Deficiency of the lipoprotein complex, surfactant, leads to RDS in the prematurely born infant. The surfactant proteins (SPs) play important roles in the function of surfactant. Previously, we identified and characterized four allelic variants of the SP-A1 gene (6A, 6A², 6A³, and 6A⁴) and five allelic variants of the SP-A2 gene (1A, 1A⁰, 1A¹, 1A², and 1A³). We hypothesized that specific alleles/genotypes are associated with increased risk of RDS. Since race, gestational age (GA), and sex are confounding factors in the etiology of RDS, we first studied the distribution and frequencies of SP-A genotypes and alleles as a function of the confounding factors in control (n=86 White, 12 Black) and RDS (n=106 White, 38 Black) populations with GA ranging from 24 wks to term (except one of 21 wks). The distributions and frequencies of SP-A1 and SP-A2 genotypes and alleles were significantly different between RDS White and Black populations, underscoring the importance of racial composition in such analyses. Although differences were observed in subgroups with different GA (≤28 wks and >28 wks) of RDS White population, due to the small sample size of ≤28 control group, definitive conclusions regarding the effect of GA could not be made. No differences were observed as a function of sex. Second, taking the above considerations into account, we compared the frequencies of SP-A genotypes and alleles between control (n=83) and RDS (n=81) in the >28 wks White population. Significant differences between the two groups were observed for 1A⁰ allele and 1A⁰/1A⁰635genotype. Also, a significant positive association was observed between 1A⁰ allele+SP-B polymorphic variants (Biochem. J. 305: 583-590, 1995) and RDS. We conclude that a) for genetic analyses of RDS and SP-A locus, the composition of control and RDS groups should be matched at least in terms of race to avoid erroneous conclusions, b) SP-A alleles/genotypes and SP-B variants may contribute to the etiology of RDS and/or may serve as markers for disease subgroups. Support by NIH HL49823, NIH HL34788.