Arginase I gene single-nucleotide polymorphism is associated with decreased risk of pulmonary hypertension in bronchopulmonary dysplasia.

Aim To test the hypothesis that there are single-nucleotide polymorphisms ( SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension ( PH) in neonates with bronchopulmonary dysplasia ( BPD). Methods Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case ( BPD + PH) and control ( BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies ( MAF) of cases and controls were compared using χ2 and logistic regression. Results Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases ( MAF = 0.23) than controls ( MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD. Conclusion Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates with BPD. [ABSTRACT FROM AUTHOR]