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Effect of the IP10 (CXCL10) and HLA genotype on the risk of type 1 diabetes in children

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Author(s): Izabela Klich | Wojciech Fendler | Krystyna Wyka | Wojciech Młynarski

Journal: Pediatric Endocrinology, Diabetes and Metabolism
ISSN 2081-237X

Volume: 17;
Issue: 1;
Start page: 10;
Date: 2011;
Original page

Keywords: type 1 diabetes | children

ABSTRACT
Introduction: Chemokines may modulate autoimmunity through a variety of mechanisms. Recent reports suggest involvement of the IP10 (CXCL10) chemokine in autoimmunity towards pancreatic β cells. Aim of the study: The purpose of this study was to evaluate the effects of genetic variability of IP10 and its dependence on HLA-conferred risk of diabetes. Materials and methods: 148 children with type 1 diabetes and 105 healthy adult controls were evaluated. Both groups underwent HLA and IP10 genotyping at rs8878. This polymorphic site is a tagging SNP of a haploblock encompassing the whole 3? untranslated region of the IP10 gene. Results: T allele homozygosity was protective against type 1 diabetes (Odds Ratio (OR) 0.48 (95% confidence interval (95%CI) 0.23-0.99). No conditional interaction effect was observed in carriers of the T allele (T+) with high risk HLA genotypes: OR(95%CI)=0.65 (0.86-1.68) for DQ2*T+ genotype and OR(95%CI)=1.20 (0.37-1.16) for DQ8*T+ genotype respectively. An interaction effect promoting earlier onset of diabetes was observed in individuals with DQ8*T+ genotypes. In these patients diabetes was diagnosed at a mean age of 5.1 (95%CI 3.3-6.8) in comparison to 9.0 (95%CI 7.6-10.4) years in patients with other genotypes (p=0.03). Conclusions: Genetic variability of the IP10 gene may play a varied role depending on the inherent genetic risk of autoimmunity. IP10 (CXCL10) variability may reduce the risk of type 1 diabetes or alter its course depending on HLA background.

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