Nakwan Narongsak, Kunhapan Punna, Chaiyasung Tassamonwan, Satproedprai Nusara, Singkhamanan Kamonnut, Mahasirimongkol Surakameth, Charalsawadi Chariyawan
Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Department of Pediatrics, Hat Yai Medical Education Center, Hat Yai Hospital, Songkhla, Thailand.
Transl Pediatr. 2023 Jan 31;12(1):1-12. doi: 10.21037/tp-22-280. Epub 2023 Jan 16.
There is known to be significant genetic involvement in persistent pulmonary hypertension of the newborn (PPHN), but to date there is not a clear understanding of this situation, and clarifying that involvement would be of considerable assistance in devising effective treatments for the disease. This case-control study was undertaken to search for genetic variants associated with PPHN in the Thai population using a genome-wide association study (GWAS).
A 659,184 single nucleotide polymorphisms from 387 participants (54 PPHN cases and 333 healthy participants) were genotyped across the human genome using an Illumina Asian Screening Array-24 v1.0 BeadChip Array. After quality control, we obtained 443,063 autosomal SNPs for the GWAS analysis. The FaST-LMM and R packages were used for all statistical analyses.
For the case-control analysis, the genomic inflation factor (λ) was 1.016, rs149768622 T>C in the first intron of gene showed the strongest association with a P value of 3.76E-08 and odds ratio (OR) of 13.24 (95% CI: 3.91-44.78). The variants at the /, , , , , , , , , and loci showed suggestive evidence of associations with PPHN (P<1E-05).
This GWAS found that rs149768622 T>C in the gene was possibly associated with PPHN. However, replication and functional studies are needed to validate this association and further explore the role(s) of the gene in PPHN.
已知新生儿持续性肺动脉高压（PPHN）存在显著的遗传因素参与，但迄今为止对这种情况尚无清晰的认识，明确这种参与情况将对设计该疾病的有效治疗方法有很大帮助。本病例对照研究旨在通过全基因组关联研究（GWAS）寻找泰国人群中与PPHN相关的基因变异。
使用Illumina亚洲筛选阵列-24 v1.0芯片对387名参与者（54例PPHN病例和333名健康参与者）的659,184个单核苷酸多态性进行全基因组基因分型。经过质量控制后，我们获得443,063个常染色体单核苷酸多态性用于GWAS分析。所有统计分析均使用FaST-LMM和R软件包。
在病例对照分析中，基因组膨胀因子（λ）为1.016，基因第一个内含子中的rs149768622 T>C显示出最强的关联，P值为3.76E-08，比值比（OR）为13.24（95%可信区间：3.91-44.78）。在/、、、、、、、、和位点的变异显示出与PPHN相关的提示性证据（P<1E-05）。
本GWAS发现基因中的rs149768622 T>C可能与PPHN相关。然而，需要进行重复验证和功能研究来证实这种关联，并进一步探索该基因在PPHN中的作用。
