Bioengineering Department, Faculty of Chemical and Metallurgical Engineering, Yıldız Technical University, Davutpasa, Istanbul, Turkey.
Neonatal Intensive Care Unit, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, Istanbul, Turkey.
Pediatr Res. 2022 Sep;92(3):888-898. doi: 10.1038/s41390-021-01851-6. Epub 2021 Dec 1.
Genetic variants contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to evaluate the association of 45 SNPs with BPD susceptibility in a Turkish premature infant cohort.
Infants with gestational age <32 weeks were included. Patients were divided into BPD or no-BPD groups according to oxygen need at 28 days of life, and stratified according to the severity of BPD. We genotyped 45 SNPs, previously identified as BPD risk factors, in 192 infants.
A total of eight SNPs were associated with BPD risk at allele level, two of which (rs4883955 on KLF12 and rs9953270 on CHST9) were also associated at the genotype level. Functional relationship maps suggested an interaction between five of these genes, converging on WNT5A, a member of the WNT pathway known to be implicated in BPD pathogenesis. Dysfunctional CHST9 and KLF12 variants may contribute to BPD pathogenesis through an interaction with WNT5A.
We suggest investigating the role of SNPs on different genes which are in relation with the Wnt pathway in BPD pathogenesis. We identified eight SNPs as risk factors for BPD in this study. In-silico functional maps show an interaction of the genes harboring these SNPs with the WNT pathway, supporting its role in BPD pathogenesis.
NCT03467828.
It is known that genetic factors may contribute to the development of BPD in preterm infants. Further studies are required to identify specific genes that play a role in the BPD pathway to evaluate them as a target for therapeutic interventions. Our study shows an association of BPD predisposition with certain polymorphisms on MBL2, NFKBIA, CEP170, MAGI2, and VEGFA genes at allele level and polymorphisms on CHST9 and KLF12 genes at both allele and genotype level. In-silico functional mapping shows a functional relationship of these five genes with WNT5A, suggesting that Wnt pathway disruption may play a role in BPD pathogenesis.
遗传变异可导致支气管肺发育不良（BPD）。本研究旨在评估在土耳其早产儿队列中，45 个 SNP 与 BPD 易感性的关联。
纳入胎龄<32 周的婴儿。根据出生后 28 天的氧需求将患者分为 BPD 或非 BPD 组，并根据 BPD 的严重程度进行分层。我们对 192 名婴儿的 45 个 SNP 进行了基因分型，这些 SNP 先前被确定为 BPD 的危险因素。
共有 8 个 SNP 与 BPD 风险相关，其中两个 SNP（位于 KLF12 的 rs4883955 和位于 CHST9 的 rs9953270）在基因型水平上也相关。功能关系图谱表明，这 5 个基因之间存在相互作用，汇聚到 WNT 通路中的 WNT5A 上，WNT5A 已知与 BPD 的发病机制有关。功能失调的 CHST9 和 KLF12 变体可能通过与 WNT5A 的相互作用导致 BPD 的发病机制。
我们建议研究与 Wnt 通路有关的不同基因上的 SNP 在 BPD 发病机制中的作用。在这项研究中，我们确定了 8 个 SNP 作为 BPD 的危险因素。基于基因的功能图谱表明，这些 SNP 所在的基因与 WNT 通路存在相互作用，支持其在 BPD 发病机制中的作用。
NCT03467828。
已知遗传因素可能导致早产儿发生 BPD。需要进一步的研究来确定在 BPD 途径中起作用的特定基因，以评估它们作为治疗干预的靶标。我们的研究表明，在等位基因水平上，MBL2、NFKBIA、CEP170、MAGI2 和 VEGFA 基因上的某些多态性以及 CHST9 和 KLF12 基因上的等位基因和基因型水平上的多态性与 BPD 易感性相关。基于基因的功能图谱表明，这五个基因与 WNT5A 之间存在功能关系，这表明 Wnt 通路的破坏可能在 BPD 的发病机制中起作用。
