The results are suggestive of an association of a synonymous SNP in the ABCA3 gene with a prolonged course of respiratory distress syndrome in very premature infants and serve as a reference for further population-based studies of ABCA3.
In contrast to lethal neonatal RDS resulting from homozygous or compound heterozygous ABCA3 mutations, single ABCA3 mutations are overrepresented among European-descent infants ≥34 weeks' gestation with RDS and account for ~10.9% of the attributable risk among term and late preterm infants.
Our data provide evidence that ABCA3 mutations are associated not only with a deficiency of ABCA3 but also with an abnormal processing and routing of SP-B and SP-C, leading to severe alterations of surfactant homeostasis and respiratory distress syndrome.
The aim of this study was to analyze eight single-nucleotide polymorphisms (SNPs) of the ABCA3 gene, and to assess the ABCA3 gene as a candidate gene for susceptibility to RDS in newborns.
Using a tagging SNP (tSNP) strategy and real-time polymerase chain reaction, we genotyped four tSNPs (i.e., rs150929, rs4787273, rs11867129, and rs17135889) and one coding SNP (p.F353F) of the ABCA3 gene in preterm infants with RDS (n = 83) and without RDS (n = 83).We predicted the haplotypes.
Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients.
Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure.
Our objective was to functionally characterize two ABCA3 mutations (p.R288K and p.R1474W) identified among term and late-preterm infants with respiratory distress syndrome with unclear pathogenicity in a genetically versatile model system.
Ventilatory treatment of neonatal respiratory distress often results in bronchopulmonary dysplasia from congenital surfactant deficiency due to mutants of transporter protein ABCA3.
In contrast to rare, nonsynonymous ABCA3 mutations, synonymous ABCA3 variants do not increase the risk for neonatal RDS among term and late-preterm infants of European or African descent.
Positive findings indicate the implication of genetic polymorphisms of proinflammatory cytokines in premature birth; angiotensin converting enzyme in perinatal adaptation and angiotensin type 1 receptor in the closure of ductus arteriosus; surfactant proteins A and B in respiratory distress syndrome; interleukin (IL)-6 in sepsis, and IL-4-receptor alpha chain and IL-18 in NEC.