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Polymorphism of monocyte chemoattractant protein 1 in Crohn's disease
Hans Herfarth1, Michael Göke, Claus Hellerbrand
1Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany. hans.herfarth@klinik.uni-regensburg.de
Background And Aims:
The chemokine MCP-1 is thought to be important for the recruitment of mononuclear cells and the maintenance of inflammation in inflammatory bowel disease. We investigated whether MCP-1 protein expression is correlated with the degree of mucosal inflammation in patients with Crohn's disease. Furthermore, we studied whether a functional single nucleotide polymorphism (G or A) located in the distal regulatory region of the MCP-1 gene is associated with Crohn's disease and/or its phenotype.
Patients And Methods:
MCP-1 concentration in tissue homogenates was analyzed in mucosal biopsy specimens of 31 patients with Crohn's disease and 48 controls by enzyme-linked immunosorbent assay, and the correlation with an endoscopic macroscopic score was analyzed. In 179 patients with Crohn's disease and 189 controls MCP-1 genotyping was carried out by polymerase chain reaction restriction fragment length polymorphism technique. Subgroup phenotypic analysis was performed according to the Vienna classification.
Results:
MCP-1 tissue concentrations were significantly associated with the macroscopic degree of inflammation. The gene frequency of the different MCP-1 alleles did not differ from healthy controls. However, the G/A and G/G genotype was significantly decreased in patients with a later onset of the disease and both genotypes presented also less frequently with a fistulizing disease behavior.
Conclusion:
The degree of intestinal inflammation in Crohn's disease is associated with MCP-1 tissue levels. Furthermore there is evidence for an association of different disease behavior with different MCP-1 genotypes.