title: Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population.
abstract: BACKGROUND
  Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans. STAT4 is involved in the signalling of interleukin-12 and γIFN, as well as interleukin-23. To discover genes affecting the susceptibility of common autoimmune diseases, we studied the association of polymorphisms in STAT4 with autoimmune thyroid disease (AITD) as well as T1D in the Korean population.
  
  
  METHODS
  Four single-nucleotide polymorphisms on the chromosome 2q (rs11889341, rs7574865, rs8179673, and rs10181656), which were found to associate with rheumatoid arthritis were examined for association in a Korean sample of 428 AITD, 418 T1D patients, and 1060 controls.
  
  
  RESULTS
  The minor alleles of all four single-nucleotide polymorphisms and the reconstructed STAT4 haplotypes conferred significant degree of risk for AITD (p=10(-2) to 10(-4)). Although we found a weak association of rs11889341 with T1D (p<0.05), the same haplotypes were not associated with T1D susceptibility. When we stratified T1D patients according to the age of onset, the minor alleles of all four single-nucleotide polymorphisms and the same haplotypes showed significant association with the susceptibility of T1D in the early-onset subgroup (p<0.01), not in the late-onset subgroup.
  
  
  CONCLUSIONS
  STAT4 alleles and the same haplotypes might influence cytokine signalling, and therefore the development of AITD as well as T1D. These results reinforce the influence of STAT4 gene as a general autoimmune gene.
authors: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, and Hanyang University Hospital, Seoul, Korea. parkys@hanyang.ac.kr
authors: Yongsoo
authors: Y
authors: Park
authors: Hye-Soon
authors: HS
authors: Lee
authors: Youngjoo
authors: Y
authors: Park
authors: Dongsoo
authors: D
authors: Min
authors: Seiwon
authors: S
authors: Yang
authors: Dukhee
authors: D
authors: Kim
authors: Boyoun
authors: B
authors: Cho
mesh_terms: D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006239:Haplotypes; D050031:Hashimoto Disease / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor / Q000235:genetics*; D013959:Thyroid Diseases / Q000235:genetics* / Q000276:immunology
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human