Assuntos
Cromossomos Humanos Par 2 , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Leucêmica da Expressão Gênica , Hidrazinas/uso terapêutico , Carioferinas/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/genética , Triazóis/uso terapêutico , Apoptose , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Hidrazinas/farmacologia , Leucemia Linfocítica Crônica de Células B/genética , Triazóis/farmacologia , Proteína Exportina 1RESUMO
The autoimmune thyroid diseases (AITDs) are multifactorial diseases which result from interplays between predisposing genes and triggering environmental factors. In order to study the genetic susceptibility factors to AITDs, we have followed up 115 control members belonging to a large Tunisian family with a high prevalence of AITDs (Akr family) during 15 years between 1990 to 2005. The follow-up of these control members have showed that 13 subjects (11.3%) developed AITDs (G2). The Hashimoto thyroiditis was the most frequently seen in 77% of the cases, whereas the Graves's disease was present in 23% of the cases. One hundred and two members remained controls (G1). High female predominance was noted in the two groups. The mean age of the G1 subjects group was slightly higher than that of G2. The prevalence of positive antithyroglobulin antibody (TgAb) and antithyroperoxydase antibody (TPOAb) was more frequent in G2 group (P=0.27 and P=0.23) respectively. The HLA haplotypes was realized in 42% of control members. The most frequent HLA haplotypes that were found were B37, DRB11 and A1. HLA B37 and DRB11 were significantly more frequent for the patients of G2 (P=0.0001 and P=0.034) respectively. Our study confirms the contribution of the genetic factors in the development of AITDs in 'Akr' family and suggested that the members of this family share the same genetic inheritance.
Assuntos
Doença de Graves/epidemiologia , Doença de Hashimoto/epidemiologia , Mixedema/epidemiologia , Adolescente , Adulto , Autoanticorpos/sangue , Feminino , Predisposição Genética para Doença , Doença de Graves/sangue , Doença de Graves/genética , Antígenos HLA/análise , Doença de Hashimoto/sangue , Doença de Hashimoto/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mixedema/sangue , Mixedema/genética , Prevalência , Hormônios Tireóideos/sangue , Tireotropina/sangue , Tunísia/epidemiologia , Adulto JovemRESUMO
The autoimmune thyroid diseases (AITDs) including Graves' disease and Hashimoto's thyroiditis are inherited as complex traits. We have performed linkage and association studies to investigate the role of CTLA-4 gene in the AITDs development using the D2S311, D2S143, the intragenic CTLA-4 (AT)(n) microsatellite markers and the CTLA-4 (A/G) dimorphism in exon 1. Four extended pedigrees belonging to a large Tunisian family named Akr and including 154 individuals from which 20 were affected with Hashimoto's thyroiditis and 26 with Graves' disease, were used in this investigation. No evidence for linkage with none of the markers was found under neither dominant nor recessive models [Z=-7.14 and Z=-14.32 at theta=0.0, respectively for the CTLA-4 (AT)(n) marker]. A family-based association study on 51 nuclear families derived from the Akr pedigree was performed by the FBAT approach applied 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 results showed no evidence for the involvement of the CTLA-4 locus in the AITDs pathogenesis.