title: Effect of the IP10 (CXCL10) and HLA genotype on the risk of type 1 diabetes in children.
abstract: BACKGROUND
  Chemokines may modulate autoimmunity through a variety of mechanisms. Recent reports suggest involvement of the IP10 (CXCL10) chemokine in autoimmunity towards pancreatic β cells.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the effects of genetic variability of IP10 and its dependence on HLA-conferred risk of diabetes.
  
  
  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.
authors.affiliation: Department of Pediatrics, Medical University of Lodz, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Klich
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.forename: Krystyna
authors.initials: K
authors.lastname: Wyka
authors.forename: Wojciech
authors.initials: W
authors.lastname: Młynarski
mesh_terms: D000293:Adolescent; D000328:Adult; D015551:Autoimmunity / Q000235:genetics*; D054357:Chemokine CXCL10 / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens