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 bacterial 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 polymorphism 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 polymorphism 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 polymorphism of the CD14 gene at -159T plays a significant role in regulating the CD14 expression and is positively associated with ulcerative colitis, and this polymorphism 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.
Obana
N
N
Dept of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. nobana@int3.med.tohoku.ac.jp
Takahashi
S
S
Kinouchi
Y
Y
Negoro
K
K
Takagi
S
S
Hiwatashi
N
N
Shimosegawa
T
T
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics*; D016001:Confidence Intervals; D003424:Crohn Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012680:Sensitivity and Specificity
D018950:Lipopolysaccharide Receptors