The autoimmune thyroid disease (AITDs) comprises two clinical phenotype, Graves disease (GD) and autoimmune hypothyroidism (AIH), which include goitrous [Hashimoto thyroiditis (HT)] and non goitrous forms [Primary idiopathic myxoedema (PIM)]. These disorders are characterized by loss of immunological self tolerance including the presence of a thyroid lymphocytic infiltrate and autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO). Inheritance of AITDs is complex and, most likely, due to the occurrence of multiple susceptibility genes and the existence of environmental factors modulating their effect. Genetic factors associated with AITDs have been tentatively identified by candidate gene and genome scanning approaches. We enrolled 12 members from multiplex Tunisian family, with high prevalence of AITDs. Nine members were affected with AITDs. Genome wide linkage scan was performed using 395 highly polymorphic markers with an average spacing of 10 cM. Statistical analysis was performed using the non parametric Lod score (NPL) test of Merlin software. Three regions were identified on chromosomes 5q13, 12q24 and 18q21 with a non parametric lod score (NPL) above 2.0. The most significant NPL in this pedigree, was obtained at marker D12S79 (NPL=3.68, P=0.0001). However, no linkage was found with microsatellite markers spanning the HLA system as well as candidate genes (CTLA-4, PTPN22, Tg, TCR Cβ and Ig VH) and AITDs. the analysis of 20 additional microsatellite markers flanking D12S79, gives significant NPL for seven markers (D12S1341, D12S354, D12S1718, D12S1612, D12S340, D12S1639 and D12S1675) (NPL>3.0, P=0.0001). Ours findings provide evidence for susceptibility locus for AITDs on chromosome 12q21-24 by use of a genome wide approach and support the existence of genetic heterogeneity in AITDs.
18 - 21 May 2019
European Society of Endocrinology