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Recent studies have suggested associations between certain genetic variants and susceptibility to persistent pulmonary hypertension of the newborn (PPHN). The aim of the study was to evaluate the association of  EDN1, NOS3, ACE  and  VEGFA  genes with PPHN. Neonates with respiratory distress were enrolled in the study, whose gestational age ≥34 weeks, age ≤3 days. They were divided into PPHN and non-PPHN group. The  EDN1, NOS3, ACE  and  VEGFA  genes were detected by next-generation sequencing, and the results were validated by Sanger sequencing. Serum endothelin-1 (ET-1) levels were quantified by ELISA. A total of 112 neonates were enrolled (n = 55 in PPHN group; n = 57 in non-PPHN group). There is a significantly difference in the genotype distribution of  EDN1  rs2070699 between the PPHN and non-PPHN group ( P  = 0). A higher frequency of the rs2070699 T allele was observed in the PPHN group (54.5% vs 27.2%; OR = 3.89; 95%CI 1.96–7.72). The rs2070699 T allele was associated with higher ET-1 levels (3.333 ± 2.517 pg/mL vs 1.223 ± 0.856 pg/mL;  P  = 0.002) and a longer ventilation period (5.8 ± 2.6 days vs 3.6 ± 3.3 days;  P  = 0). The results suggest there is an association between  EDN1  and PPHN. The presence of the rs2070699 T allele increased the risk of PPHN in neonates with respiratory distress.

EDN1 Gene Variant is Associated with Neonatal Persistent Pulmonary Hypertension