Ulcerative colitis is associated with a promoter polymorphism of lipopolysaccharide receptor gene, CD14

Background: Inflammatory bowel disease (IBD) is a multifactorial disease with a significant genetic background. Evidence is accumulating that molecules such as CD14, which interact with luminal bacteria l constituents, are involved in the pathogenesis. It has recently been shown that the T allele of the 5'-flanking region of the CD14 gene at position - 159 is related to high expression of CD14. In further exploring the genetic background of IBD, we investigated this novel polymorphis m of CD14 gene in patients with ulcerative colitis or Crohn disease. Methods: DNA was obtained from 101 patients with ulcerative colitis, 82 with Crohn disease and 123 healthy controls. All were typed for the promoter polymorphism of the CD14 gene at position - 159 by restriction fragment length polymorphis m analysis. Serum samples were obtained from 105 healthy controls and serum sCD14 levels were measured. Results: T allele frequencies were 57.4%, 48.2% and 44.7% in ulcerative colitis, Crohn disease and healthy controls, respectively. The T allele and T/T genotype frequencies were significantly higher in ulcerative colitis patients than in healthy controls (P = 0.0074, OR = 1.67, 95% CI = 1.15-2.42, P = 0.022, OR = 1.96 95% CI: 1.10-3.48, respectively). The sCD14 level was significantly higher in TT genotype populations than CC (P = 0.0205). Conclusions: The promoter polymorphis m of the CD14 gene at - 159T plays a significant role in regulating the CD14 expression and is positively associated with ulcerative colitis, and this polymorphis m may confer a genetic predisposition to ulcerative colitis. The results also support the concept that bacterial constituents may be involved in the pathogenesis of ulcerative colitis.