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- Title
Interaction of HLA-DRB1 Alleles with CTLA-4 in the Predisposition to Graves' Disease: The Impact of DRB1*07.
- Authors
Dorota Kula; Tomasz Bednarczuk; Beata Jurecka-Lubieniecka; Joanna Polanska; Kornelia Hasse-Lazar; Michal Jarzab; Katarzyna Steinhof-Radwanska; Beata Hejduk; Jadwiga Zebracka; Alina Kurylowicz; Ewa Bar-Andziak; Tomasz Stechly; Agnieszka Pawlaczek; Elzbieta Gubala; Aleksandra Krawczyk; Sylwia Szpak-Ulczok; Janusz Nauman; Barbara Jarzab
- Abstract
Objective: To study interactions between the two most widely confirmed Graves’ disease (GD) loci: HLA-DRB1and CTLA-4. HLA-DRB1∗03 (risk allele) and DRB1∗07 (protective allele) were analyzed in this aspect, the linkedTNF G(-308)A polymorphism was also considered. Design: A case-control study of 429 patients with GD comparedto 308 healthy subjects. The impact of genes and their interactions were analyzed by stepwise logistic regression.Results: The independent effects of DRB1∗03 and DRB1∗07 were confirmed in our study both by stratificationstudies and logistic regression. CTLA-4 did not appear to be associated with GD when the interactionswith other genes were considered. By logistic regression we observed a significant interaction between DRB1∗07and CTLA-4 and revealed that CTLA-4 49G attenuated the DRB1∗07-related protection, the effect noticed alsoin three-way stratification studies. We confirmed that the TNF G(–308)A polymorphism is only a marker ofthe DRB1 status. Conclusion: Our results stress the importance of complex gene interactions in the multigenepredisposition to GD. The interactions between two predisposing loci, DRB1 and CTLA-4, are exerted ratherby DRB1∗07 than DRB1∗03 allele: CTLA-4 acts via switching off the protective DRB1∗07 influence, whereas theeffect of DRB1∗03 is independent.
- Subjects
GRAVES' disease; GENETIC polymorphisms; PATIENTS; GENES
- Publication
Thyroid, 2006, Vol 16, Issue 5, p447
- ISSN
1050-7256
- Publication type
Article