Narongsak Nakwan, Punna Kunhapan, Tassamonwan Chaiyasung, Nusara Satproedprai, Kamonnut Singkhamanan, Surakameth Mahasirimongkol, Chariyawan Charalsawadi
Prince of Songkla University. Hat Yai Hospital. Ministry of Public Health.
Thailand
Translational Pediatrics
Transl Pediatr 2023;
DOI: 10.21037/tp-22-280
Abstract
Background: 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).
Methods: 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.
Results: For the case-control analysis, the genomic inflation factor (λ) was 1.016, rs149768622 T>C in the first intron of WWC2 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 LOC102723906/LOC105377599, CADM4, GPM6A, CIT, RIMBP2, LOC105374510, LOC105375193, PTPRN2, CDK14, and LCORL loci showed suggestive evidence of associations with PPHN (P<1E-05).
Conclusions: This GWAS found that rs149768622 T>C in the WWC2 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 WWC2 gene in PPHN.
Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes