Lack of Association between IL-12B Gene Polymorphism and Autoimmune Thyroid Disease in Japanese Patients

Ikeda, Yukio; Yoshida, Wakako; Noguchi, Tōru; Asaba, Koichi; Nishioka, Tatsuya; Takao, Toshihiro; Hashimoto, Kozo

doi:10.1507/endocrj.51.609

Cited by 21 publications

(20 citation statements)

References 37 publications

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“…We showed a significant increase in IL-12 -1188C allele and the CC genotype in patients with GD. This association does not seem to be present in Japanese [27,28] and European [29] populations. Our results regarding the association between the C allele and GD are not surprising given that IL-12 levels are elevated in the hyperthyroid phase of GD [27][28][29].…”

Section: Discussionmentioning

confidence: 63%

“…This association does not seem to be present in Japanese [27,28] and European [29] populations. Our results regarding the association between the C allele and GD are not surprising given that IL-12 levels are elevated in the hyperthyroid phase of GD [27][28][29]. IFN-c has a critical role in enhancing the expression HLA class I, class II, and some adhesion molecules on thyrocytes, including intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen-3 (LFA-3).…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

Anvari

Khalilzadeh

Esteghamati

et al. 2010

Endocr

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The role of genetic factors in the pathogenesis of Graves' disease (GD) is not clear. The purpose of this study was to investigate the association between single nucleotide polymorphisms in pro-inflammatory cytokine genes and GD in Iranian patients. A case-control hospital-based study was carried out on 107 GD patients and 140 healthy controls. Cytokine typing was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The allele and genotype frequencies of the following cytokine genes were determined: TNF-α (-308A/G, -238A/G), IL-2 (-330T/G, +166G/T), IL-6 (-174C/G, A/G nt565), IL-12 (-1188A/C), and IFN-γ (UTR 5644A/T). The following alleles and genotypes were significantly overrepresented in patients: TNF-α -308A allele (P < 0.01) and AA genotype (P < 0.05), IL-2 -330G allele (P < 0.01) and GG genotype (P < 0.01), IL-6 -174C allele (P < 0.01) and CC genotype (P < 0.01), IL-12 -1188C allele (P < 0.01) and CC genotype (P < 0.01), IFN-γ UTR5644T allele (P < 0.01) and TT genotype (P < 0.01). In conclusion, this is the first study to show a significant association between GD and IL-2 -330G, IL-12 -1188C, and IFN-γ UTR 5644T alleles. Our results support the hypothesis that polymorphism in pro-inflammatory cytokines might be involved in predisposition to GD.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 63%

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

Anvari

Khalilzadeh

Esteghamati

et al. 2010

Endocr

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“…Therefore, we hypothesized that IL-12B gene might be a potential candidate gene contributing to the development of GD or influencing its clinical severity and course, especially GO. Recently, Ikeda et al [39] performed a genetic association study using 90 GD patients and 123 control subjects in Japanese. They could not find any association between the IL-12B gene polymorphisms (A/T polymorphism in the intron 4 or 1188A/C in the 3'UTR) and GD.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction -restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

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“…Similarly, the IL-12p40 polymorphism did not seem to play a major role on genetic susceptibility to autoimmune thyroid diseases in a Japanese population. [29,30] However, when we analysed the serum levels of IL12p40 in HT patients and controls according to the genotype of 3'UTR A/C IL12B polymorphisms, we found significantly higher serum level of IL-12p40 for the AA genotype in HT in comparison with AA healthy individuals. On the basis of this finding, it could be supposed that the carriers of the AA genotype of IL12B, with their higher production if Il-12, may more frequently develop HT.…”

Section: Resultsmentioning

confidence: 80%

Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

Gerenova

Manolova

Stanilova

2016

Biotechnology & Biotechnological Equipment

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Hashimoto's thyroiditis (HT) is an organ-specific, mainly Th1 autoimmune disorder. New evidence has accumulated for involvement of Treg-produced cytokines. Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with antagonistic effect on Th differentiation. This study was designed to investigate the correlation of circulating IL-10 and IL-12p40 with their genotypes in 124 HT patients in different stages of disease. The IL-10 and IL-12p40 circulating level in the serum of HT patients and healthy controls was determined by enzyme-linked immunosorbent assay. Genotyping for the 3'UTR A/C IL12B polymorphism was performed using restriction fragment length polymorphismÀpolymerase chain reaction and genotyping for ¡1082 A/G by amplification refractory mutation system (ARMS)-PCR. The results showed significantly enhanced IL-12p40 serum quantity both in euthyroid and hypothyroid stages compared to controls and insignificantly decreased level after levothyroxine treatment. Regarding the 3'UTR A/C IL12B polymorphism, a significantly higher frequency of the AA genotype was observed in HT patients than in healthy individuals. The serum IL-10 level was significantly increased in hypothyroid HT patients compared to controls and euthyroid patients. Stratification based on the ¡1082 A/G polymorphism revealed a significantly enhanced level of circulating IL-10 in hypothyroid patients with a GG genotype compared to AA and AG genotypes. There were also significant differences between the circulating IL-10 quantity in hypo-and euthyroid patients with GG genotypes. In conclusion, the IL-12p40 and IL-10 serum level in HT patients was dependent on the genotype and HT stages, suggesting that enhanced IL-10 serum level in combination with enhanced IL-12p40 is associated with hypothyroidism in HT development.

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Lack of Association between IL-12B Gene Polymorphism and Autoimmune Thyroid Disease in Japanese Patients

Cited by 21 publications

References 37 publications

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

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