The −590CC Genotype in the IL4 Gene as a Strong Predictive Factor for the Development of Hypothyroidism in Hashimoto Disease

Nanba, Takashi; Watanabe, Mikio; Akamizu, Takashi; Iwatani, Yoshinori

doi:10.1373/clinchem.2007.099739

Cited by 45 publications

(27 citation statements)

References 4 publications

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“…However, the IL-1b -31C/T polymorphism was not associated with the severity of HD (Table 1), suggesting no association between the genetic producibility of IL-1b and the severity of HD. This indicates that, in contrast to IFN-g, IL-4 and TGF-b1 [5][6][7], IL-1b may have a minor effect on the severity of autoimmune thyroid destruction in HD.…”

Section: Discussionmentioning

confidence: 98%

“…Some HD patients develop hypothyroidism in early life, and some maintain a euthyroid state in old age, despite the passage of time [3,4]. Although the immunological differences that underlie the differences in intractability or severity remain unclear, we have reported that the +874T allele of IFNG gene, which has a higher producibility of interferon (IFN)-g, the +869C allele of the TGFB1 gene, which has a lower producibility of transforming growth factor (TGF)-b1, and the -590C allele of IL4 gene, which has a lower producibility of interleukin (IL)-4 are involved in the severe destruction of thyroid tissue in HD [5][6][7], and that functional polymorphisms in the TNFA gene encoding tumour necrosis factor (TNF)-a are associated with the development of AITD and the levels of thyrotrophin receptor antibody (TRAb) in active GD patients [8].…”

Section: Introductionmentioning

confidence: 99%

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Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

Hayashi

Watanabe

Nanba

et al. 2009

Clinical and Experimental Immunology

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SummaryInterleukin (IL)-1b is a proinflammatory cytokine and has been implicated in the pathogenesis of several autoimmune diseases. To evaluate the hypothesis that the functional -31C/T polymorphism (rs1143627) in the gene encoding IL-1b is associated with the intractability and the severity of autoimmune thyroid diseases, we genotyped this polymorphism in 64 patients with intractable Graves' disease (GD), 28 GD patients in remission, 49 patients with Hashimoto's disease (HD) who developed hypothyroidism (severe HD), 28 untreated euthyroid HD patients (mild HD) and 59 healthy volunteers. The -31T allele, which is related to the high producibility of IL-1b, was significantly more frequent in patients with intractable GD than in those with GD in remission (P = 0·0017; odds ratio 2·8; 95% confidence interval 1·5-5·3), although there was no difference in this frequency between two groups of HD patients. We showed additionally that the proportion of IL-17-producing T helper type 17 (Th17) cells, whose differentiation and proliferation are promoted by IL-1b, was higher in autoimmune thyroid disease patients with the T allele than in those with CC genotypes. In conclusion, our data indicated that the T allele of -31C/T polymorphism in the IL1B gene was involved in the intractability of GD, and this involvement may arise through the differentiation and proliferation of Th17 cells.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

Hayashi

Watanabe

Nanba

et al. 2009

Clinical and Experimental Immunology

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“…The literature search yielded 8 articles on rs2243250 [11,12,14,15,[35][36][37][38], 4 on rs2070874 [15,35,38,39], and 1 each on rs2234248 [38], rs2243288, rs2243289, and rs2243290 [15]. The genotype distribution in all studies conformed to Hardy-Weinberg equilibrium except in that of Khalilzadeh et al [38] (p Ͻ 0.001), which was then excluded from further analysis.…”

Section: Meta-analysismentioning

confidence: 99%

Association of an IL-4 gene haplotype with Graves disease in children: experimental study and meta-analysis

et al. 2011

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“…Progression from subclinical hypothyroidism to overt hypothyroidism typically develops over a period of several years and occurs at a rate of ~5% a year; the presence of either subclinical hypothyroidism or raised thyroid antibodies indicates an increased risk of overt hypothyroidism and the risk is greater when these factors occur together (14). In Hashimoto's disease, both Th1 and Th2 responses are found (15), although with different reciprocal intensity in relationship with the clinical expression of the disease process (16)(17)(18). However, recent studies have demonstrated the existence of new subpopulations of T helper cells that are also important in immunoregulation and host defense, like Treg cells and Th17 cells (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Immunological changes of T helper cells in flow cytometer‑sorted CD4+ T cells from patients with Hashimoto's thyroiditis

et al. 2018

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Abstract. Recent incidence rates for Hashimoto's thyroiditis (HT) and hypothyroidism are higher than those of previous studies. Previous studies indicated that T helper cells may have a major role in the pathogenesis and development of HT, but there is no consensus in the literature. The aim of the present study was to explore the peripheral T helper cell response in the different stages of HT. In this cross-sectional study, we performed flow cytometry analysis to determine the various T cell subsets of 389 patients with HT (34 patients with HT who developed overt hypothyroidism, and 148 patients with HT who developed subclinical hypothyroidism), as well as 51 healthy controls. Anti-thyroid antibodies, and thyroid function were measured. The findings demonstrated that the proportion of peripheral Th1 cells was significantly lower in patients with HT than in healthy euthyroid controls (P<0.001), and the proportion of peripheral Th2, Treg cells was significantly higher in patients with HT than in healthy euthyroid controls (P<0.001). Therefore the Th1/Th2 ratio was significantly lower in HT patients than in healthy euthyroid controls (P<0.001). The Th17/Treg ratio in HT patients was significantly lower than that control subjects (P<0.001). Th1 proportions in patients with overt hypothyroidism HT were significantly higher than in subclinical hypothyroidism HT patients (P=0.031). In conclusion, the findings of the present study demonstrated that there is an increased immune deviation of Th1 lymphocytes and compensatory accelerating activity of Treg cells in HT, and the peripheral Th1 cells from the HT patients correlated to the developmental stage of hypothyroidism.

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The −590CC Genotype in the IL4 Gene as a Strong Predictive Factor for the Development of Hypothyroidism in Hashimoto Disease

Cited by 45 publications

References 4 publications

Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

Association of the −31C/T functional polymorphism in the interleukin-1β gene with the intractability of Graves' disease and the proportion of T helper type 17 cells

Association of an IL-4 gene haplotype with Graves disease in children: experimental study and meta-analysis

Immunological changes of T helper cells in flow cytometer‑sorted CD4+ T cells from patients with Hashimoto's thyroiditis

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