title: Polymorphisms of interleukin-21 and interleukin-21-receptor genes confer risk for autoimmune thyroid diseases.
abstract: BACKGROUND
  The abnormality of interleukin-21 (IL-21)-IL-21-receptor (IL-21R) system has been found in many autoimmune diseases including autoimmune thyroid diseases (AITDs). In this study, we investigated whether polymorphisms of the IL-21 and IL-21R are associated with Graves' disease (GD) and Hashimoto's thyroiditis (HT), two major forms of AITDs, among a Chinese population.
  
  
  METHODS
  Rs907715, rs4833837, rs2221903 and rs2055979 of the IL-21 gene and rs3093301 and rs2285452 of the IL-21R gene were explored in a case-control study including 405 GD, 228 HT patients and 242 controls. These genes were genotyped by the PCR and restriction fragment length polymorphism (RFLP) analysis and the MASS spectrometry method.
  
  
  RESULTS
  For IL-21 gene, we identified and confirmed a higher prevalence of A alleles of rs2221903 (P = 0.018, OR = 1.50 95% CI = 1.07-2.09) in GD patients. We also found a significant association between rs2221903 and HT (allele: P = 0.009, OR = 1.69 95% CI = 1.13-2.51; genotype: recessive P = 0.021, OR = 11.72 95% CI = 1.46-94.13). For the IL-21R gene, compared with controls, the genotype frequencies of rs3093301 and rs2285452 were significantly different in HT patients using dominant genetic model (P = 0.023, OR = 1.61 95% CI = 1.07-2.42; P = 0.031, OR = 1.71 95% CI = 1.05-2.80, respectively). Furthermore, the haplotype AA containing the major alleles of rs4833837 and rs2221903 was associated with increased susceptibility to GD with an OR of 1.50(95% CI =1.08-2.09, P = 0.016), and to HT with an OR of 1.69(95% CI =1.14-2.52, P = 0.009).
  
  
  CONCLUSIONS
  Our results indicated that the SNPs of the IL-21 gene is associated with the development of GD. In addition, we found that individuals with the SNPs of the common IL-21 and IL-21R may have higher risk of HT.
authors.affiliation: Endocrinology Department, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, China. zhangjinan@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Wan Xia
authors.initials: WX
authors.lastname: Xiao
authors.forename: Yuan Feng
authors.initials: YF
authors.lastname: Zhu
authors.forename: Fatuma Said
authors.initials: FS
authors.lastname: Muhali
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.forename: Wen Juan
authors.initials: WJ
authors.lastname: Jiang
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Shi
authors.forename: Lian Hua
authors.initials: LH
authors.lastname: Zhou
authors.forename: Jin An
authors.initials: JA
authors.lastname: Zhang
references.citation: Scand J Immunol. 2006 Nov;64(5):515-22
references.pmid: 17032244
references.citation: Genes Immun. 2008 Jun;9(4):364-7
references.pmid: 18418394
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11439-44
references.pmid: 11016959
references.citation: Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007 Feb;23(2):124-6
references.pmid: 17286904
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Nat Rev Immunol. 2005 Sep;5(9):688-98
references.pmid: 16138102
references.citation: Gut. 2009 Jun;58(6):799-804
references.pmid: 19201773
references.citation: World J Gastroenterol. 2010 Aug 7;16(29):3638-41
references.pmid: 20677335
references.citation: Genes Immun. 2010 Mar;11(2):194-8
references.pmid: 20072139
references.citation: PLoS Genet. 2011 Aug;7(8):e1002216
references.pmid: 21829393
references.citation: Am J Hum Genet. 2007 Dec;81(6):1284-8
references.pmid: 17999365
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1518-23
references.pmid: 19164519
references.citation: Ann Rheum Dis. 2008 Apr;67(4):458-61
references.pmid: 17720724
references.citation: Tissue Antigens. 2009 Sep;74(3):244-7
references.pmid: 19523143
references.citation: PLoS Genet. 2008 Mar 28;4(3):e1000041
references.pmid: 18369459
references.citation: Genet Mol Res. 2011 Oct 31;10(4):3338-46
references.pmid: 22057994
references.citation: Nature. 2000 Nov 2;408(6808):57-63
references.pmid: 11081504
references.citation: Hum Mol Genet. 2009 Nov 1;18(21):4219-25
references.pmid: 19648293
references.citation: Arthritis Rheum. 2009 Aug;60(8):2402-7
references.pmid: 19644854