A 20 year history of clinical and genetic study of thyroid autoimmunity in a Tunisian multigenerational family: Evidence for gene interaction()

Autoimmune thyroid diseases (AITD), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized by their clinical and genetic heterogeneity. In this study, we have carried on a global approach gathering 20 year genetic and clinical data on a Tunisian multigenerational family (Akr). Our purpose was search for a combined genotype involved in AITD susceptibility using 33 gene polymorphisms. The Akr pedigree is composed of more than 400 members distributed on 10 generations. Clinical follow-up was performed by appreciation of the thyroid gland and measurement of both thyroid hormone and auto antibody levels. We used FBAT software to test for association between gene polymorphisms and AITDs. Clinical follow-up has showed that the number of AITD patients has increased from 25 to 78 subjects subdivided on 51 cases of GD, 22 PIM and 5 HT. Concerning genetic analysis, our study has revealed new gene association when compared with our previous analysis (considering single genes). Thus, PTPN22, TG and VDR gene polymorphisms have became associated with p-values ranging from 4.6 10(− 2) to 4 10(− 3) when considered with other genes on the same chromosome; giving evidence for gene interaction. The most significant association was found with the MHC region (p = 7.15 10(− 4)). Moreover, and among gene polymorphisms explored, our analysis has identified some of them as AITD biomarkers. Indeed, PDS gene polymorphisms were associated with either exophthalmia or goiter (p-values from 10(− 2) to 10(− 3)). In conclusion, our study gives evidence for gene interaction in AITD development confirming genetic complexity of these diseases.