A full genome screening in a large Tunisian family affected with thyroid autoimmune disorders

Abstract

The autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are inherited as complex traits. We initiated a whole genome linkage study of patients with AITD, in order to identify the susceptibility genes involved in their pathogenesis. We studied 39 patients affected with GD or HT and 68 related controls, who belonged to a large consanguinous family composed of more than 200 members. Linkage analysis was performed using the lod score method under two arbitrary models, one dominant and one recessive. A positive lod score was found for D2S171, assuming a recessive mode of inheritance and 50% penetrance, which suggests the presence of a major AITD susceptibility gene on chromosome 2p21. However, no linkage was found with microsatellite markers spanning the HLA system. This locus localised outside MHC will be of interest for investigation of other autoimmune disorders. Genes and Immunity (2001) 2, 71-75.

CTLA-4 Gene Polymorphisms in Tunisian Patients with Graves' Disease

“…In our population, linkage analysis of CTLA-4 gene polymorphisms in a large Tunisian consanguineous family didn't show any role for this gene in the development of AITD (24,37). In this work, we found an association between CTLA-4 (AT) n and CTLA-4 A/G polymorphisms and GD.…”

“…Recently, evidence for varying degrees of genetic linkage have been reported between autoimmune thyroid disease (AITD) and markers on the long arms of chromosomes 14q31, 20q11, Xq21, 20q13, and 18q21 (11, 18 -21) and on the short arms of chromosomes Xp11 (22) and 6 close to, but distinct from, the human leukocyte antigen region (23). A full genome screening in a large Tunisian family affected with AITD showed a linkage with the D2S171 microsatellite marker in the 2p21 chromosome (24). These studies are still waiting for confirmation in different populations.…”

Hashimoto's Disease

“…In Tunisian population, genome screening, performed on Akr family, has revealed a genetic linkage of AITDs as a whole with the chromosomal region 2p.21. There were no regions linked to HT (Maalej et al, 2001a).…”

“…One of the large multiplex families in the world was reported in Tunisia (Akr family) (Maalej, A. et al 2001a). The high prevalence of both GD and HT, found in the "Akr" family (17.5%), is another argument to the contribution of genetic factors in HT pathogenesis.…”

“…We will also focus on epidemiology, clinical progression and physiopathological mechanism of the disease. We will shed light on our findings concerning a Tunisian multigenerational family "Akr" (Maalej et al, 2001a) which has benefited from a regular clinical follow-up, a complex segregation analysis as well as a genetic investigation using both genome screening and candidate genes approaches.…”