Open AccessDDAH1 SNP rs480414 that protects against the development of pulmonary hypertension in bronchopulmonary dysplasia results in lower nitric oxide production in neonatal cord blood-derived lymphoblastoid cell lines
Author(s) -
Avante D Milton,
Hanadi Almazroue,
Y. Jin,
Gloria Zender,
Jennifer K. Trittmann
Publication year - 2022
Publication title -
journal of neonatal-perinatal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.444
H-Index - 17
eISSN - 1934-5798
pISSN - 1878-4429
DOI - 10.3233/npm-210710
Subject(s) - asymmetric dimethylarginine , nitric oxide , snp , sodium nitroprusside , bronchopulmonary dysplasia , apoptosis , andrology , medicine , biology , single nucleotide polymorphism , biochemistry , arginine , gestational age , genetics , amino acid , pregnancy , gene , genotype
Bronchopulmonary dysplasia (BPD) is chronic lung disease of prematurity and pulmonary hypertension (PH) is a major contributor to morbidity and mortality in BPD patients. Nitric oxide (NO) is a vasodilator and apoptotic mediator made by NO synthase (NOS). NOS is inhibited by asymmetric dimethylarginine (ADMA), and dimethylarginine dimethylaminohydrolase (DDAH) hydrolyzes ADMA. Previously, in a BPD patient cohort, we identified single nucleotide polymorphism (SNP) DDAH1 rs480414 (G > A) that was protective against developing PH. This study aims to determine functional consequences of the DDAH1 SNP in lymphoblastoid cell lines (LCLs) derived from neonatal cord blood. We tested the hypothesis that DDAH1 SNP (AA) results in DDAH1 gain of function, leading to greater NO-mediated apoptosis compared to DDAH1 wild-type (GG) in LCLs.