Susceptibility role of soluble HLA-G and HLA-G 14-bp insertion/deletion polymorphism in inflammatory bowel disease

Abstract

Abstract Background Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract. It is fundamentally related to a dysregulated immune response in the intestinal mucosa against microbiota in genetically predisposed individuals. Among the genetic and immunological factors that are suggested to have role in etiology and pathogenesis of IBD are human leukocyte antigen (HLA)-G molecules. Therefore, soluble HLA-G (sHLA-G) serum level and genetic association with HLA-G 14-bp insertion (Ins)/deletion (Del) polymorphism was analyzed in 100 IBD patients; 50 ulcerative colitis (UC) and 50 Crohn’s disease (CD), and 100 controls. Results sHLA-G level was significantly elevated in IBD patients compared to controls (174.7 ± 27.1 vs. 126.8 ± 15.1; corrected probability [pc] < 0.001). The level was also elevated in UC patients compared to CD patients but the difference was not significant (180.5 ± 27.1 vs. 168.9 ± 26.3; p = 0.059). Receiver operating characteristic analysis confirmed the significance of sHLA-G in total IBD, UC, and CD patients (area under curve = 0.944, 0.961, and 0.927, respectively). The genetic association was analyzed under five genetic models (allele, recessive, dominant, overdominant, and codominant). At the allele level, Del allele frequency was significantly increased in total IBD patients (Odds ratio [OR] = 1.93; 95% confidence interval [CI] = 1.27–2.94; pc = 0.018) and CD patients (OR = 2.08; 95% CI = 1.23–3.54; pc = 0.042) compared to controls. Among UC patients, a similar increased frequency was observed, but the pc value was not significance (OR = 1.79; 95% CI = 1.07–3.00; p = 0.031). At the genotypic level, Del/Del genotype was associated with a significantly increased IBD-risk in total patients under codominant model (OR = 4.06; 95% CI = 1.56–10.56; pc = 0.024). sHLA-G level was not influenced by the Ins/Del polymorphism. Conclusions This study demonstrated a significant increase in serum level of sHLA-G in UC and CD patients. Further, HLA-G 14-bp Ins/Del polymorphism may be associated with susceptibility to IBD, particularly CD.