A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes

presence of the SDFI-3'A allele was associated with a 5-year reduction in t he age at onset of diabetes (P = Type 1 diabetes results from the autoimmun e destruction of pancreatic beta -cells. Although the disease shows a stron g association with HLA class II alleles, other genes may influence the init iation or the rate of progression of the autoimmune process. The recruitmen t of mononuclear cells within the islets of Langerhans is a critical step i n the pathogenesis of the disease. Because chemokines are cytokines that pr omote migration of mononuclear cells, we hypothesized that polymorphisms in chemokine receptor or chemokine genes, CCR5 and SDF1, may be involved in s usceptibility to or clinical expression of type 1 diabetes. The frequencies of the CCR5-Delta 32 and SDF1-3'A (801G -->A in the 3' untranslated region ) variants were similar in 208 unrelated Caucasian patients with type 1 dia betes and in 120 Caucasian control subjects. They were ndt modified after s tratification for the predisposing HLA-DR3 and -DR4 haplotypes, However, th e SDF1-3'A variant was strongly associated with early onset (<15 years) of the disease (odds ratio 2.6, P = 0.0019), On average, the presence of the S DF1-3'A allele was associated with a 0.0067), Our results suggest that stro mal cell-derived factor-1 may be implicated in the aggressiveness of the au toimmune process leading to type 1 diabetes, These preliminary data require replication in other populations.