Association of functional polymorphisms in promoter regions ofIL5, IL6andIL13genes with development and prognosis of autoimmune thyroid diseases

Abstract

SummaryTo clarify the association of genetic producibility of interleukin (IL)-5, IL-6 and IL-13, which are secreted by T helper type 2 (Th2), with the development and prognosis of autoimmune thyroid disease (AITD), we genotyped IL5 -746C/T, IL6 -572C/G and IL13 -1112C/T polymorphisms, which are functional polymorphisms in the promoter regions of the genes regulating these cytokines. Fifty-seven patients with intractable Graves' disease (GD), 52 with GD in remission, 52 with severe Hashimoto's disease (HD), 56 with mild HD and 91 healthy controls were examined in this study. The IL13 -1112T allele, which correlates with higher producibility of IL-13, was more frequent in patients with GD in remission than in those with intractable GD [P = 0·009, odds ratio (OR) = 3·52]. The IL5 -746T allele, which may correlate with lower levels of IL-5, was more frequent in patients with GD in remission than controls (P = 0·029, OR = 2·00). The IL6 -572G allele carriers (CG and GG genotypes), which have higher producibility of IL-6, were more frequent in AITD patients (P = 0·033, OR = 1·75), especially in GD in remission (P = 0·031, OR = 2·16) and severe HD (P = 0·031, OR = 2·16) than in controls. Interestingly, both allele and genotype frequencies of Th2 cytokine genes were similar between GD and HD patients. In conclusion, functional polymorphisms in the genes encoding Th2 cytokines are associated differently with the development and prognosis of AITD from each other.

The combination of ınterleukin-10 −1082 and tumor necrosis factor α −308 or ınterleukin-6 −174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis

“…With regard to some clinical phenotypes of patients with HT, it has been shown previosly that presense of variant allele of an other polymorphic locus in the promoter region of IL-6 gene (C-572G SNP) is associated with prognosis of HT [20], and that −857 T allele of TNFα gene is associated with increased antibody production in Graves' disease [11]. However, in our study no correlations were obtained between genotype at TNFα G-308A, IL-6 G-174C and IL-10 G-1082A polymorphisms and clinical phenotypes of HT patients.…”

“…Several single nucleotide polymorphisms (SNPs) in the regulatory regions of TNFα, IL-6 and IL-10 have been implicated to modulate the risk of autoimmune diseases, possibly by influencing the expression of the protein [11][12][13][14][15][16][17][18][19][20] and could be critical to the etiology of HT.…”

Lack of Association between theIL-13 C-1112T, G2044APolymorphisms and Graves’ Disease Risk: Evidence from a Meta-analysis

“…Figure 1 showed the process of identifying eligible studies. A total of seven studies were included in this meta-analysis (Bednarczuk et al, 2003;Chong et al, 2008;Hiromatsu et al, 2005;Inoue et al, 2011;Simmonds et al, 2005;Yang et al, 2005;Zhu et al, 2010). Among them, six studies investigated the C-1112T polymorphism (Bednarczuk et al, 2003;Chong et al, 2008;Hiromatsu et al, 2005;Inoue et al, 2011;Simmonds et al, 2005;Yang et al, 2005), whereas five studies assessed the G2044A polymorphism (Bednarczuk et al, 2003;Chong et al, 2008;Hiromatsu et al, 2005;Simmonds et al, 2005;Zhu et al, 2010).…”

Contribution of CD24 polymorphisms to autoimmune disease: A meta-analysis

“…MS and HLA-DRB1, HLA-DR2, the IL-2 receptor gene, and IL-1; and RA and IL-18, IRF5, and PTPN22 [10][11][12][13][14][15][16][17][18][19].…”