Genetic associations of surfactant protein D and angiotensin-converting enzyme with lung disease in preterm neonates

Objective: To replicate genetic associations with respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in genes related to surfactant deficiency, inflammation and infection, and the renin-angiotensin system. Study Design: We examined eight candidate genes for associations with RDS and BPD in 433 preterm birth (PTB-<37 weeks) infants (251 with RDS and 134 with BPD). Both case-control and family-based analyses were performed in preterm (<37 weeks) and very preterm birth (VPTB-<32 weeks) infants. Result: We replicated a previous finding that rs1923537, a marker downstream of surfactant protein D (SFTPD) is associated with RDS in VPTB infants in that the T allele was overtransmitted from parents to offspring with RDS (P = 8.4 x 10(-3)). We also observed the A allele of rs4351 in the angiotensin-converting enzyme (ACE) gene was overtransmitted from parents to VPTB offspring with BPD (P = 9.8 x 10(-3)). Conclusion: These results give further insight into the genetic risk factors for complex neonatal respiratory diseases and provide more evidence of the importance of SFTPD and ACE in the etiology of RDS and BPD, respectively. Journal of Perinatology (2012) 32, 349-355; doi:10.1038/jp.2011.104; published online 29 September 2011