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 ( SNP s) 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 SNP s in l ‐arginine/nitric oxide pathway genes by S equenom massarray. Genes included carbamoyl‐phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNP s were selected from the N ational C enter for B iotechnology I nformation database for their putative functionality. Calculated minor allele frequencies ( MAF ) of cases and controls were compared using χ 2 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 SNP s, 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 .