Interaction of HLA-DRB1 Alleles with CTLA-4 in the Predisposition to Graves' Disease: The Impact of DRB1*07
| Autor: | Kornelia Hasse-Lazar, Agnieszka Pawlaczek, Tomasz Bednarczuk, Alina Kurylowicz, Tomasz Stechly, Jadwiga Zebracka, Joanna Polanska, Beata Jurecka-Lubieniecka, Ewa Bar-Andziak, Janusz Nauman, Sylwia Szpak-Ulczok, Barbara Jarzab, Elzbieta Gubala, Michal Jarzab, Beata Hejduk, Katarzyna Steinhof-Radwanska, Dorota Kula, Aleksandra Krawczyk |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Risk musculoskeletal diseases Endocrinology Diabetes and Metabolism Graves' disease Disease Logistic regression Endocrinology Antigens CD immune system diseases Polymorphism (computer science) medicine Humans CTLA-4 Antigen Genetic Predisposition to Disease Allele skin and connective tissue diseases HLA-DRB1 Alleles Polymorphism Genetic business.industry HLA-DR Antigens Middle Aged Stepwise regression medicine.disease Antigens Differentiation Graves Disease Logistic Models CTLA-4 Immunology Female business HLA-DRB1 Chains |
| Zdroj: | Thyroid. 16:447-453 |
| ISSN: | 1557-9077 1050-7256 |
| Popis: | To study interactions between the two most widely confirmed Graves' disease (GD) loci: HLA-DRB1 and CTLA-4. HLA-DRB1*03 (risk allele) and DRB1*07 (protective allele) were analyzed in this aspect, the linked TNF G(-308)A polymorphism was also considered.A case-control study of 429 patients with GD compared to 308 healthy subjects. The impact of genes and their interactions were analyzed by stepwise logistic regression.The independent effects of DRB1*03 and DRB1*07 were confirmed in our study both by stratification studies and logistic regression. CTLA-4 did not appear to be associated with GD when the interactions with other genes were considered. By logistic regression we observed a significant interaction between DRB1*07 and CTLA-4 and revealed that CTLA-4 49G attenuated the DRB1*07-related protection, the effect noticed also in three-way stratification studies. We confirmed that the TNF G(-308)A polymorphism is only a marker of the DRB1 status.Our results stress the importance of complex gene interactions in the multigene predisposition to GD. The interactions between two predisposing loci, DRB1 and CTLA-4, are exerted rather by DRB1*07 than DRB1*03 allele: CTLA-4 acts via switching off the protective DRB1*07 influence, whereas the effect of DRB1*03 is independent. |
| Databáze: | OpenAIRE |
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