Association of TNF-alpha, TNF-beta, IFN-gamma and IL-1Ra gene polymorphisms with Graves' disease in the Thai population.

Cytokines play a key role in the regulation of immune and inflammatory responses. Therefore, cytokine genes are potentially related to susceptibility to Graves' disease (GD). The aim of this study was to investigate the putative functional polymorphisms within tumor necrosis factor-alpha (TNF-alpha), tumor necrosis factor-beta (TNF-beta), interferon-gamma (IFN-gamma), and interleukin-1 receptor antagonist (IL-1Ra) genes, in patients with GD (n = 137) compared to a healthy Thai control group (n = 137). The results showed no statistically significant difference between the study groups for TNF-beta (Ncol site in intron 1), IFN-gamma (+874 in intron 1), and IL-1Ra (variable numbers of tandem repeats in intron 2) gene polymorphisms. Only the -863A allele within the promoter region of the TNF-alpha gene, which may affect the affinity of the promoter nuclear factor (NF)-kappab interaction, was found to be increased in GD patients compared to the controls (p = 0.009, OR = 1.8, 95% CI = 1.15 to 2.84). The effect of the -863A allele of the TNF-alpha gene was similar to the autosomal dominance mode of inheritance (p = 0.01, OR = 2, 95% CI = 1.16 to 3.44). This polymorphism may be involved in the susceptibility to GD in part through its higher promoter activity of TNF-alpha production.

No association between an interleukin 4 gene promoter (-589) polymorphism and Graves' disease in Thai patients.

Cytokines play a key role in the regulation of immune and inflammatory responses and therefore are potential candidate genes for autoimmune thyroid disease. Polymorphisms in cytokine genes may effect gene transcription, causing individual variations in cytokine production. Several investigators have linked the interleukin-4 (IL-4) gene and autoimmune disease. The present population-based study was to investigate the polymorphisms of IL-4 gene promoter (-589C/T) in GD patients compared with a control group and determine the association with GD in a Thai population. The subjects included 137 GD patients and 137 healthy control subjects with similar ethnic and geographic backgrounds. The IL-4 gene polymorphism at position -589 in the promoter was analyzed using the PCR-RFLP. The protective effect of the -589T allele as suggested by Hunt et al in a Caucasian population was not observed in the present study. The -589T allele frequencies were similar between patients and control subjects (69% vs 69.3%) suggesting that this polymorphism can not be used as a genetic marker for GD susceptibility in Thais.