title: IL12RB2 gene is associated with the age of type 1 diabetes onset in Croatian family Trios.
abstract: BACKGROUND
  Common complex diseases are influenced by both genetic and environmental factors. Many genetic factors overlap between various autoimmune diseases. The aim of the present study is to determine whether four genetic variants known to be risk variants for several autoimmune diseases could be associated with an increased susceptibility to type 1 diabetes mellitus.
  
  
  RESULTS
  We genotyped four genetic variants (rs2358817, rs1049550, rs6679356, rs9865818) within VTCN1, ANXA11, IL12RB2 and LPP genes respectively, in 265 T1DM family trios in Croatian population. We did not detect association of these polymorphisms with T1DM. However, quantitative transmission disequilibrium test (QTDT, orthogonal model) revealed a significant association between the age of onset of T1DM and IL12RB2 rs6679356 variant. An earlier onset of T1DM was associated with the rs6679356 minor dominant allele C (p = 0.005). The association remained significant even after the Bonferroni correction for multiple testing and permutation.
  
  
  CONCLUSIONS
  Variants originally associated with juvenile idiopathic arthritis (VTCN1 gene), sarcoidosis (ANXA11 gene), primary biliary cirrhosis (IL12RB2 gene) and celiac disease (LPP gene) were not associated with type 1 diabetes in our dataset. Nevertheless, association of IL12RB2 rs6679356 polymorphism with the age of T1DM onset suggests that this gene plays a role in defining the time of disease onset.
authors.affiliation: Department of Medical Biology, University of Split, School of Medicine, Split, Croatia. marina.pehlic@mefst.hr
authors.forename: Marina
authors.initials: M
authors.lastname: Pehlić
authors.forename: Dina
authors.initials: D
authors.lastname: Vrkić
authors.forename: Veselin
authors.initials: V
authors.lastname: Skrabić
authors.forename: Ana
authors.initials: A
authors.lastname: Jerončić
authors.forename: Gordana
authors.initials: G
authors.lastname: Stipančić
authors.forename: Anita Špehar
authors.initials: AŠ
authors.lastname: Urojić
authors.forename: Igor
authors.initials: I
authors.lastname: Marjanac
authors.forename: Jasminka
authors.initials: J
authors.lastname: Jakšić
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Kačić
authors.forename: Vesna
authors.initials: V
authors.lastname: Boraska
authors.forename: Tatijana
authors.initials: T
authors.lastname: Zemunik
mesh_terms: D017668:Age of Onset; D000483:Alleles; D017302:Annexins / Q000235:genetics; D002648:Child; D017523:Croatia / Q000453:epidemiology; D003598:Cytoskeletal Proteins / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics
chemical_list: D017302:Annexins; D003598:Cytoskeletal Proteins; C508439:IL12RB2 protein, human; D060588:LIM Domain Proteins; C103594:LPP protein, human; D053707:Receptors, Interleukin-12; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human