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

Pediatr Res. 1999 Jul;46(1):82-4. doi: 10.1203/00006450-199907000-00014.


Studies have shown the important roles of several regulatory and proinflammatory cytokines in insulin-dependent diabetes mellitus (IDDM). CC-chemokine receptors CCR2 and CCR5 bind chemokines that are involved in the trafficking of leukocytes in both basal and inflammatory states. A common 32-bp deletion mutation in the CCR5 gene (CCR5delta32) and a G-to-A nucleotide substitution in the CCR2 at position 190 (CCR2-64I) have recently been described. In the present study, we have determined the frequency of the CCR5delta32 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]. The CCR5delta32 allele frequencies were 0.117 in children with IDDM and 0.111 in nondiabetic subjects, indicating that the deletion allele has no association 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 yet, but, because CCR2 mediates the chemotaxis of CD4+ and CD8+ T cells to areas of inflammation and because these cells play important roles in insulitis, a mutation in the CCR2 gene may contribute to the susceptibility to the disease. Alternatively, the 64I allele could be a marker of a linked mutation through linkage disequilibrium. According to these results, the CCR2 gene may be a new candidate for the susceptibility locus of IDDM. However, because no IDDM locus has been identified near 3p21 until now, further investigations are needed to confirm this statement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Alleles
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Genotype
  • Humans
  • Infant
  • Male
  • Point Mutation
  • Polymorphism, Genetic*
  • Receptors, CCR2
  • Receptors, CCR5 / genetics*
  • Receptors, Chemokine*
  • Receptors, Cytokine / genetics*
  • Reference Values
  • Sequence Deletion


  • CCR2 protein, human
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine
  • Receptors, Cytokine