Objective: The 1st exon 5' noncoding region rs1799946 (-52A/G), rs1800972 (-44C/G), rs11362 (-20A/G) 3 single-nucleotide polymorphisms (SNPs) on human β-defensin-1 (HBD-1) gene affect its transcription and posttranscriptional mRNA stability then affect the activity of HBD-1. This study was to investigate the effects of HBD-1 gene rs1799946, rs1800972, and rs11362 locus SNPs on genetic susceptibility and prognosis of acute respiratory distress syndrome (ARDS).
Methods: A total of 300 patients with ARDS (ARDS group) and 240 patients who were admitted to the intensive care unit and had a high risk of ARDS but did not progress to ARDS (control group) were included in this study. The genotypes of HBD-1 gene rs1799946, rs1800972, and rs11362 locus and serum HBD-1 were detected. Patients were followed for 60 days with development of ARDS as a primary outcome, ARDS-related mortality and organ dysfunction were secondary outcomes.
Results: HBD-1 gene rs1799946 and rs11362 gene mutations were not risk factors for ARDS (P > .05). Mutation allele G of rs1800972 locus in HBD-1 gene was a risk factor for ARDS. There was no significant difference in serum HBD-1 levels between patients with different genotypes of rs1799946 and rs11362 locus in the HBD-1 gene (P > .05). HBD-1 gene rs1800972 locus wild type, heterozygous, and mutant homozygous serum levels of HBD-1 gradually decreased, the difference was statistically significant (P < .001). The 60-day survival rate of subjects with wild type, heterozygous, and mutant homozygote at the rs1800972 locus of HBD-1 gene decreased sequentially (81.7%, 48.9%, and 39.7%), and the difference was statistically significant (P < .05).
Conclusion: The SNP of rs1800972 (-44C/G) in HBD-1 gene is associated with the risk of ARDS. The rs1800972 locus G allele carriers are more likely to develop ARDS and have a poor prognosis.