Details

Autor(en) / Beteiligte

• Ghaderi, Mehran
• Gambelunghe, Giovanni
• Tortoioli, Cristina
• Brozzetti, Annalisa
• Jatta, Ken
• Gharizadeh, Baback
• De Bellis, Annamaria
• Pecori Giraldi, Francesca
• Terzolo, Massimo
• Betterle, Corrado
• Falorni, Alberto

Titel

MHC2TA Single Nucleotide Polymorphism and Genetic Risk for Autoimmune Adrenal Insufficiency

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2006-10, Vol.91 (10), p.4107-4111

Ort / Verlag

Bethesda, MD: Endocrine Society

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Context: The polymorphism of class II HLA genes modulates the genetic risk for several endocrine autoimmune diseases. The constitutive class II expression on antigen-presenting cells is under the control of the MHC class II transactivator, encoded by the MHC2TA gene, which is mapped to chromosome 16p13. The MHC2TA −168 A→G single nucleotide polymorphism (rs3087456) has been suggested to confer susceptibility to some autoimmune diseases. Design: With the aim of testing whether this MHC2TA single nucleotide polymorphism is independently associated with autoimmune Addison’s disease (AAD) and/or modulates the genetic risk conferred by DRB1-DQA1-DQB1 haplotypes, we analyzed DNA samples from 128 AAD patients and 406 healthy control subjects from continental Italy. Results: Frequency of allele G of MHC2TA was significantly increased among AAD patients (39% alleles), compared with 29% in healthy controls (P = 0.003). Similarly, the frequency of AG+GG genotypes was significantly higher among AAD patients than among healthy control subjects, in both a codominant (P = 0.012) and a G-dominant model (P = 0.018). Multivariate logistic regression analysis showed that MHC2TA AG+GG continued to be positively associated with genetic risk for AAD (P = 0.028, odds ratio = 1.72, 95% confidence interval = 1.06–2.78), after correction for DRB1*03-DQA1*0501-DQB1*0201, DRB1*04 (not 0403)-DQA1*0301-DQB1*0302 and DRB1*0403. Similar results were obtained when the number of G alleles was included in the model (P = 0.004; odds ratio = 1.65, 95% confidence interval = 1.17–2.32). Conclusions: Our study provides the first demonstration of the association of the polymorphism of the MHC2TA gene with genetic risk for AAD that appears to be independent from the well-known association with the polymorphism of HLA class II genes.