A potential role of TNFR gene polymorphisms in autoimmune thyroid diseases in the Tunisian population.

Autoimmune thyroid diseases (AITDs) including Graves disease (GD) and autoimmune hypothyroidism (AH) are associated with TNF genes polymorphisms. TNF molecules bind to TNFRI and TNFRII. No genetic association was reported between TNFR and AITDs. In this study, we have analysed two polymorphisms in TNFRI gene (TNFRI+36A/G SNP and a microsatellite (GT)(17) (GA)(n)) and one polymorphism in TNFRII gene (TNFRII +676 T/G). All these polymorphisms were studied in a large Tunisian family with high prevalence of AITDs, and on a case-control sample of 91 GD patients and 165 controls. The present study was undertaken to investigate the genetic association of these polymorphisms with AITDs development. We reported the implication of TNFRIA3 allele in AITDs pathogenesis in familial and case control studies, respectively (chi(2)=4.13, p=0.042; chi(2)=9.26, p(c)=0.005). In addition, Case-control study has revealed for the first time that TNFRII+676G allele was associated with GD (chi(2)=11.53; p=0.0007). Two TNFRI haplotypes were found to be associated with GD: TNFRI+36G-A8, TNFRI+36A-A3 (chi(2)=88.07; p=6.32x10(-21), chi(2)=16.78; p=4.2x10(-5), respectively). Our data showed that TNFRI polymorphisms have an important role in AITDs pathogenesis in both familial and case-control samples and that TNFRII was rather implicated in GD development in the Tunisian population.