Department of Clinical Pathology-Hematology and Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, 11566, Egypt.
Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Eur J Pediatr. 2021 Sep;180(9):2831-2838. doi: 10.1007/s00431-021-04053-8. Epub 2021 Mar 27.
Persistent pulmonary hypertension of the new-borns (PPHN) is one of the main etiologies of morbidity as well as mortality in neonates. Previous studies found that genetic polymorphisms in urea cycle enzymes are associated with PPHN. Few of the genetic polymorphisms in neonates have been recognized with PPHN. We aimed to find out the prevalence of the CPS-I gene polymorphism and to correlate the genotype with the serum nitric oxide (NO) levels in Egyptian neonates with idiopathic PPHN. We included neonates diagnosed with PPH (n = 150) while the control group included healthy neonates with matched age and sex (n = 100). The CPS-I gene polymorphism: A/C, trans-version substitution, rs4399666 genotype was identified using TaqMan-based quantitative PCR. The results revealed that the CPS-I A/C rs4399666 gene polymorphism and lower serum NO levels were significantly associated with idiopathic PPHN in neonates. In addition, serum NO level was significantly associated with an rs4366999 A/C variant gene in idiopathic PPHN (p = 0.001). Univariable regression analysis demonstrated that there was a significant association between CPS-I A/C rs4399666 CC and increased risk of PPHN (odd ratio, 95% CI of 1.8 (0.78 to 1.75), p-value = 0.04).Conclusion: We concluded that mutant CPS-I A/C rs4399666 minor variant especially the homozygous CC genotype is frequently distributed among the PPHN group. This demonstrates that the presence of mutant CPS-I rs4399666 does not necessarily predispose to the development of PPHN in neonates, but nonetheless, if the C allele is inherited in the homozygous CC genotype, it is associated with a higher risk of PPHN. What is Known: • Prior studies found that polymorphisms in urea cycle enzyme genes are associated with PPHN. • Association between CPS-1 gene polymorphisms is significantly associated with PPHN. What is New: • The prevalence of CPS-1, A/C trans-version substitution, rs4399666 gene polymorphism in Egyptian neonates presented with idiopathic PPHN. • Mutant CPS-I A/C rs4399666 especially the homozygous CC genotype is more frequently distributed among PPHN, and it is significantly associated with low serum nitric oxide level.
新生儿持续性肺动脉高压（PPHN）是新生儿发病率和死亡率的主要病因之一。先前的研究发现，尿素循环酶的遗传多态性与 PPHN 有关。在新生儿中，已经认识到少数遗传多态性与 PPHN 有关。我们旨在找出 CPS-I 基因多态性的流行率，并将基因型与埃及特发性 PPHN 新生儿的血清一氧化氮（NO）水平相关联。我们纳入了诊断为 PPHN 的新生儿（n = 150），而对照组包括年龄和性别相匹配的健康新生儿（n = 100）。使用 TaqMan 定量 PCR 鉴定 CPS-I 基因多态性：A/C、转换替代、rs4399666 基因型。结果表明，CPS-I A/C rs4399666 基因多态性和血清 NO 水平较低与新生儿特发性 PPHN 显著相关。此外，血清 NO 水平与特发性 PPHN 中的 rs4366999 A/C 变体基因显著相关（p = 0.001）。单变量回归分析表明，CPS-I A/C rs4399666 CC 与 PPHN 风险增加之间存在显著关联（比值比，95%CI 为 1.8（0.78 至 1.75），p 值= 0.04）。结论：我们得出结论，突变 CPS-I A/C rs4399666 小变体，尤其是纯合 CC 基因型，在 PPHN 组中频繁分布。这表明突变 CPS-I rs4399666 的存在不一定导致新生儿 PPHN 的发生，但如果 C 等位基因以纯合 CC 基因型遗传，则与 PPHN 的风险增加相关。已知：•先前的研究发现，尿素循环酶基因的多态性与 PPHN 有关。•CPS-1 基因多态性与 PPHN 显著相关。新内容：•埃及特发性 PPHN 新生儿中 CPS-1、A/C 转换替代、rs4399666 基因多态性的流行率。•突变 CPS-I A/C rs4399666，尤其是纯合 CC 基因型，在 PPHN 中分布更为频繁，与低血清一氧化氮水平显著相关。
