The MCP-1 promoter -2518 polymorphism in Behcet's disease: correlation between allele types, MCP-1 production and clinical symptoms among Korean patients

OBJECTIVE: To compare the G vs. A variation at the MCP-1 promoter -2518 position among normal Koreans and Behcet patients, and to investigate possible association of this polymorphism with disease pathogenesis. METHODS: The allele type of -2518 polymorphism was determined by restriction fragment length polymorphism of Pvu II. The level of MCP-1 in serum and culture supernatent was measured by sandwich ELISA. RESULTS: The average serum level of MCP-1 in Behcet patients was 2.37 times higher than in normal controls. The serum MCP-1 concentration was higher in G-allele carriers than in AA homozygotes, and symptoms accompanying graver cases of Behcet's disease, such as gastrointestinal inflammation and uveitis, were more frequent in patients with the G-allele. However, the frequency of G-allele in patient group was not higher than that in healthy Koreans, probably due to the dominance of G-allele in general Korean population. When stimulated in vitro with IL-1beta and LPS, the mononuclear cells from patients carrying the G-allele showed a steeper increase in MCP-1 production than the boost observed in AA homozygotes. CONCLUSION: Although the allele frequency of MCP-1 promoter -2518 polymorphism is not likely to be the reason for the elevated serum MCP-1 level in Korean patients with Behcet's disease, it is possible that proinflammatory factors induced in patients' serum cause stronger activation of MCP-1 expression from the G-type promoter, as well as increased incidence of uveitis and gastric ulcer, among carriers of the G-allele.