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

Abstract

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.

No Association BetweenIL12BGene Polymorphisms and Graves’ Disease in the Chinese Population

“…These results mean that the IL12B gene polymorphism is an unlikely susceptibility factor for Chinese patients with GD. These results are consistent with a previous study (17,20), which suggested that the A/G polymorphism located in the 3 untranslated region of IL12B gene was not associated with Grave's disease. They are also consistent with the data of Walsh et al who found that the MAF for rs6887695 was 0.45 in GD (double that in men with Hashimoto's disease).…”

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

“…42,43 A previous study in Japan failed to show this association with GD or GO. 13 In contrast, we revealed in an Iranian population a significant increase in the frequency of the 1188C allele and CC genotype among patients with GO. Ethnic differences might explain a part of this inter-population inconsistency.…”

“…10 As proinflammatory cytokines are known to have important roles in the development of GO, 9,11,12 we investigated the hypothesis that specific polymorphisms in proinflammatory cytokine genes might contribute to the development of GO. Previous reports on the topic are limited, [13][14][15][16][17][18][19] and further studies are necessary to elucidate the issue. 20 In this study, the association of GO with the following polymorphisms in proinflammatory cytokines were evaluated in Iranian GD patients with and without GO: IL-12 (À1188A/C), TNF-a (À308A/G, À238A/G), INF-g (UTR 5644A/T), IL-2 (À330T/G, 166G/T), and IL-6 (À174C/G, nt565A/G).…”

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

“…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].…”

“…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).…”