Association analysis of IL1 gene polymorphisms in autoimmune thyroid diseases in the Tunisian population

Autoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and autoimmune hypothyroidism (AH), are inherited as complex traits. Among the genes contributing to AITD susceptibility are genes of the IL-1 family. IL-1 regulates T and B lymphocyte maturation, including the induction of several cytokines and cytokine receptors. Therefore, disturbances of this balance may not only play a role in inflammation but also in the pathogenesis of autoimmunity. In order to investigate genetic association of IL-1 gene polymorphisms with AITDs, we performed both a familial study in a large Tunisian pedigree with high prevalence of AITDs (64 patients and 176 controls), and a case-control study (131 GD, unrelated patients and 225 healthy controls). PCR and PCR-RFLP methods were used to analyse respectively a VNTR in the IL-1RN gene and three SNPs in both IL-1B genes (-511 C/T and +3954 C/T) and IL1A (-889 C/T). A family-based association study showed an association of the IL1B+3954 C/T polymorphism (p = 0.02) and two haplotypes IL1RN*3/C/T/T and IL1RN*1/C/T/T (p = 0.009 and p = 0.047 respectively) with AITDs. The case-control study is the first study revealing a significant association of the IL1A-889 C/T polymorphism (chi2 = 10.23; p = 0.0014) with susceptibility to GD.Our data suggest that the IL-1 gene cluster may harbour susceptibility genes for AITDs and GD pathogenesis in the Tunisian population.