Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus

Studies have shown the important roles of several regulatory and proinflamm atory cytokines in insulin-dependent diabetes mellitus (IDDM). CC-chemokine receptors CCR2 and CCRS bind chemokines that are involved in the trafficki ng of leukocytes in both basal and inflammatory states. A common 32-bp dele tion mutation in the CCR5 gene (CCR5 Delta 32) and a G-to-A nucleotide subs titution in the CCR2 at position 190 (CCR2-64I) have recently been describe d. In the present study, we have determined the frequency of the CCR5 Delta 32 and CCR2-64I alleles in children with IDDM [n = 115; age 1-14 (9.3 +/- 4.3) y] and in nondiabetic subjects [n = 280; age 1-14 (8.5 +/- 4.5) y]. Th e CCR5 Delta 32 allele frequencies were 0.117 in children with IDDM and 0.1 11 in nondiabetic subjects, indicating that the deletion allele has no asso ciation with IDDM. The CCR2-64I allele frequency in children with IDDM was 0.226, which differed significantly from the allele frequency in controls ( 0.114, p = 0.001). The role of this mutation in IDDM cannot be explained ye t, but, because CCR2 mediates the chemotaxis of CD4+ and CD8+ T cells to ar eas of inflammation and because these cells play important roles in insulit is, a mutation in the CCR2 gene may contribute to the susceptibility to the disease. Alternatively, the 641 allele could be a marker pf a Linked mutat ion through linkage disequilibrium. According to these results, the CCR2 ge ne may be a new candidate for the susceptibility locus of IDDM. However, be cause no IDDM locus has been identified near 3p21 until now, further invest igations are needed to confirm this statement.