Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus.
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.
Szalai
C
C
Heim Pál Pediatric Hospital, Budapest, Hungary.
Császár
A
A
Czinner
A
A
Szabó
T
T
Pánczél
P
P
Madácsy
L
L
Falus
A
A
D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics*; D012016:Reference Values; D017384:Sequence Deletion
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine