Influence of promoter polymorphism in the CD14 gene on the course of Crohn's disease

Background: CD14 (LPS receptor) interacts with luminal bacterial constituents and plays a signal role in the release of cytokines. A functionally relevant C(-159)T polymorphism in the promoter region of CD14 is associated with several diseases, but the role of this polymorphism in CD is controversial.

The aim of our study was to investigate the frequency of C/T CD14 polymorphism in CD with different types of severity in comparison with ethnically matched healthy controls.

Material and methods: Blood samples from 143 CD patients and 75 blood donors were collected; all clinical data on the patients were registered. The CD patients were divided into two groups, depending on the course of the disease: mild, if neither operation nor immunosuppressive treatment was applied, or severe, if any of the above-mentioned features was positive. C(-159)T polymorphism was investigated by restriction fragment length polymorphism analysis. Genotype frequencies were compared by means of chi-squared testing. Results: The frequency of TT homozygotes was higher in the CD group, than in the controls. The difference displayed a strong tendency toward the significance in each behaviour subtype of CD versus controls (p=0.08). The TT homozygote mutation was significantly more frequent in the operated CD patients (33% vs. 22%, p=0.0369). The occurrence of the TT homozygote genotype was significantly higher in severe than in mild CD (29% vs. 20%, p=0.0015) or in the control group (29% vs. 20% p=0.0041); there was no difference between the mild CD group and the controls.

Conclusion: A single nucleotide mutation of the promoter region of the CD 14 gene seems to be associated with a more severe disease course in CD. An altered immune response to bacterial LPS may influence the disease severity in CD.