RGD Reference Report - Chemokine receptor CCR2 and CCR5 polymorphisms in children with insulin-dependent diabetes mellitus. - Rat Genome Database

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

Authors: Szalai, C  Csaszar, A  Czinner, A  Szabo, T  Panczel, P  Madacsy, L  Falus, A 
Citation: Szalai C, etal., Pediatr Res. 1999 Jul;46(1):82-4.
RGD ID: 2313564
Pubmed: PMID:10400139   (View Abstract at PubMed)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR2Humantype 1 diabetes mellitus  IAGP DNA:polymorphism: :p.V64I (human)RGD 
Ccr2Rattype 1 diabetes mellitus  ISOCCR2 (Homo sapiens)DNA:polymorphism: :p.V64I (human)RGD 
Ccr2Mousetype 1 diabetes mellitus  ISOCCR2 (Homo sapiens)DNA:polymorphism: :p.V64I (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information