Lack of linkage and association between autoimmune thyroid diseases and the CTLA-4 gene in a large Tunisian family

The autoimmune thyroid diseases (AITDs) including Graves' disease and Hashi moto's thyroiditis are inherited as complex traits. We have performed linka ge and association studies to investigate the role of CTLA-4 gene in the AI TDs development using the D2S311, D2S143, the intragenic CTLA-4 (AT)(n) mic rosatellite markers and the CTLA-4 (A/G) dimorphism in exon 1. Four extende d pedigrees belonging to a large Tunisian family named Akr and including 15 4 individuals from which 20 were affected with Hashimoto's thyroiditis and 26 with Graves' disease, were used in this investigation. No evidence for l inkage with none of the markers was found under neither dominant nor recess ive models [Z = -7.14 and Z = -14-32 at theta = 0.0, respectively for the C TLA-4 (AT)(n) marker]. A family-based association study on 51 nuclear famil ies derived from the Akr pedigree was performed by the FBAT approach applie d to the CTLA-4 (AT)(n) marker and the CTLA-4 (A/G) dimorphism. We found no association of individual alleles to disease for both markers. These resul ts showed no evidence for the involvement of the CTLA-4 locus in the AITDs pathogenesis. (C) American Society for Histocompatibility and Immunogenetic s, 2001. Published by Elsevier Science Inc.