The role of intragenic and intergenic combinations of SFTPB and SFTPC gene polymorphisms in the pathogenesis of respiratory distress syndrome and bronchopulmonary dysplasia in preterm newborns

Genetic polymorphisms of surfactant proteins SP-B and SP-C may contribute to the development of respiratory disorders among preterm newborns. The aim of this study was to analyze the contribution of intergenic and intragenic combinations of SFTPB and SFTPC genotypes to the pathogenesis of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants. A total of 567 newborns were genotyped for the polymorphic loci rs2077079 and rs1130866 of the SFTPB gene as well as rs4715, rs1124, and rs2070687 of the SFTPC gene using real-time PCR with TaqMan probes and Sanger sequencing. In preterm girls, the risk of RDS was significantly higher in those carrying the genotype combinations –18CCSFTPB/413CASFTPC and –18CCSFTPB/436-8CGSFTPC (p = 0.044 and p = 0.03, respectively). The 1580СТSFTPB/ 557ААSFTPC combination was associated with severe RDS regardless of sex (p = 0.019). Among girls, RDS severity was linked to –18CASFTPB/557CCSFTPC and 1580CT/–18CA SFTPB combinations ( p = 0.018 and p = 0.033, respectively), while in boys, the 1580TTSFTPB/413CCSFTPC combination was associated with more severe disease (p = 0.03). In preterm infants with a gestational age of 28–34 weeks, the risk of BPD was associated with the 1580СТSFTPB/413ССSFTPC genotype combination ( p = 0.031). Thus, specific intergenic and intragenic combinations of SFTPB and SFTPC gene polymorphisms are significantly associated with the risk and severity of RDS and BPD in preterm newborns.