Association of High Mobility Group Box Protein B1 Gene Polymorphisms with Pneumonia Susceptibility and Severity.

Abstract

To investigate the relationship between the high mobility group box protein B1 (HMGB1) single nucleotide polymorphisms (SNPs) rs1412125, rs2249825, and rs1045411 with pneumonia in terms of susceptibility, severity, and inflammatory response. The genotypes of HMGB1 rs1412125 (-1615T > C), rs2249825 (3814C > G), and rs1045411 (2262C > T) loci in 328 patients with community-acquired pneumonia (CAP) and 317 healthy subjects were analyzed by Sanger sequencing. The expression and secretion of the inflammatory cytokines HMGB1, interleukin (IL)-10, tumor necrosis factor-alpha (TNF-α), and IL-6 were determined after lipopolysaccharide (LPS) stimulation of peripheral whole blood cells. The risk of CAP was higher in carriers of the mutant HMGB1 rs1412125 and rs2249825 alleles than those that had the wild type alleles (adjusted odds ratio [OR] = 1.241; 95% confidence interval [CI] = 1.061-1.448; p = 0.007; adjusted OR = 1.225; 95% CI = 1.038-1.427; p = 0.016, respectively). Moreover, the mutation-carrying patients with CAP were more likely to develop severe community-acquired pneumonia (SCAP). There was no correlation between the HMGB1 rs1045411 SNP alleles and CAP or SCAP (p > 0.05). The expression and secretion of the inflammatory cytokines HMGB1, IL-10, TNF-α, and IL-6 was significantly higher in LPS-stimulated peripheral blood among patients with mutations at the rs1412125 and rs2249825 loci compared with those with wild type alleles (p < 0.05). The 30-day mortality rates for CAP patients with mutations at the rs1412125 and rs2249825 loci of HMGB1 were significantly higher than those that had wild type alleles. The mortality rate difference between rs1045411 wild-type CAP patients and mutant was not significant (p = 0.789). SNPs at the rs1412125 and rs2249825 loci of HMGB1 are associated with pneumonia in terms of susceptibility, severity, and inflammatory response.