Association between functional polymorphisms in the nitric oxide synthase 3 gene and pediatric acute respiratory...

Nitric oxide mediates multiple physiological functions, including neurotransmission, immune regulation, angiogenesis, antiplatelet activity, and surfactant maturation or secretion. Mice deficient in the nitric oxide synthase 3 (NOS3) gene displayed defective lung vascular development and fatal respiratory distress. Polymorphisms in NOS3 have been reported to be associated with respiratory distress syndrome (RDS). The role of NOS3 polymorphisms as a risk factor for pediatric acute respiratory distress syndrome (PARDS) was evaluated by analyzing the possible functional single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of NOS3. Samples from 216 PARDS patients and 225 healthy control subjects were genotyped at 4 SNP loci (rs11771443 and rs3918188 in the promoter region, rs1799983 in exon 7, and rs7830 at the intron24-exon23 boundary). Statistically significant differences were observed in the allelic or genotypic frequencies of the rs1799983 and rs11771443 polymorphisms in NOS3. The T and G alleles of rs1799983 and rs11771443 were associated with a significantly higher risk of PARDS compared to the C allele (P = 0.030) and the T allele (P = 0.004), respectively. Strong linkage disequilibrium was observed in one block (D' > 0.9). Subjects with PARDS displayed significantly fewer T-C haplotypes (P = 0.013) in block 1 (rs1799983-rs11771443). These findings indicate that NOS3 polymorphisms play a definitive role in PARDS, and therefore may be useful for future genetic or neurobiological studies on RDS.