Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome

Background: The etiology of respiratory distress syndrome (RDS) is multifactorial and/or multigenic. Surfactant protein A (SP-A) and/or SP-B genetic variants have been identified as risk or protection factors for RDS. Methods: We genotyped subjects with and without RDS for the SP-B intron 4 size variants (invariant (inv), deletion (del), insertion (ins) and for four (-18 (A/C), 1013 (A/C), 1580 (C/T), 9306 (A/G)) SP-B single nucleotide polymorphisms (SNP), to study case-control associations in black and white subjects. We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS. Results: Based on odds ratio: (1) the SP-B intron 4 del variant in white subjects is more of an RDS risk factor for males and for subjects of 28 weeks < gestational age (GA) < 33 weeks; (2) the SP-B intron 4 ins variant in black subjects is more of an RDS risk factor in females; (3) in white subjects, SP-A1 (6A²/6A²) or SP-A2 (1A⁰/1A⁰ or 1A⁰/*) genotypes in subjects of certain GA and with a specific SP-B genotype (9306 (A/G) or del/*) are associated with an enhanced risk for RDS; (4) in black subjects, SP-A1 (6A³/6A³ or 6A³/*) genotypyes in subjects of 31 weeks ≤ GA ≤ 35 weeks and with the SP-B (1580 (T/T)) genotype are associated with a reduced risk for RDS. Conclusions: The SP-B polymorphisms are important determinants for RDS. These may identify differences between black and white subjects, as well as, between males and females regarding the risk for RDS. Furthermore, SP-A susceptibility or protective alleles, in specific SP-B background, are associated, based on OR, with an increased or reduced risk for RDS.