Evidence for linkage and association between autoimmune thyroid diseases and the 18q12-q21 region in a large Tunisian family.

Many studies have shown linkage between IDDM6 locus on 18q12-q21 chromosome and several autoimmune diseases, suggesting that it might harbour susceptibility genes common to autoimmunity. Using 12 families deriving from a large Tunisian multiplex family (the Akr family) from which 38 people were affected with autoimmune thyroid diseases (AITD), and 193 unrelated AITD patients, tested against 100 healthy subjects, we tried to replicate the positive results previously reported for the IDDM6. Akr members were genotyped with eight microsatellite markers harbouring the IDDM6 region. Multipoint non-parametric linkage analysis have shown a clear peak values of NPL score around D18S41 marker (Z = 3.72, P = 0.0001). Family-based association test (FBAT) and transmission disequilibrium test (TDT) have confirmed linkage results. In particular, a significant association with allele 3 of D18S41 and allele 2 of D18S57 markers was found. Case-control studies, using one intragenic microsatellite (locus CTG18.1) marker in the immunoglobulin transcription factor (ITF2) gene, a 5' flanking AC repeat of the anti-apoptotic BCL-2 gene as well as two SNPs at positions +52 and +1955 from transcription start site of BCL-2, showed no significant association between neither genes and AITD. Our study is the first replication of the 18q12-q21 chromosome region as a potential candidate to AITD genetic susceptibility. The Akr family has shown evidence for linkage between IDDM6 locus and AITD. Moreover, case-control study does not support the involvement of ITF2 and BCL2 genes in AITD pathogenesis.