A GENETIC PROFILE IDENTIFIES THE RISK FOR GRAVES' DISEASE AND CLINICAL FEATURES ASSOCIATED TO ITS EVOLUTION
Presentation Number: OR28-3
Date of Presentation: June 16th, 2013
Natássia Elena Bufalo1, Angélica Gomes Rocha1, Roberto Bernando Santos2, Joao Hamilton Romaldini2 and Laura Sterian Ward*3
1University of Campinas, Campinas, Brazil, 2Pontifical Catholic University of Campinas, Campinas, Brazil, 3University of Campinas, Campinas,SP, Brazil
Genetic predisposition to Graves’ disease (GD) involves important immunoregulatory genes such as CTLA-4, PTPN22, CD40, and thyroid specific genes such as TSHR. However, their role in the predisposition to GD, its clinical presentation and response to therapy remains unclear. Using TaqMan SNP Genotyping®, we genotyped 282 GD patients (234 females and 48 males, 39.80 ± 11.69 years old; 153 treated with radioiodine, 123 with antithyroid drugs and 6 with surgery; followed up for 61±38 months; 138 patients presented clinical evidence of eye involvement) and 308 healthy individuals paired for age, gender and ethnicity. A multivariate analysis demonstrated that the inheritance of a CTLA-4 CT60 GG genotype increased the risk for GD (OR=2.36; 95%CI=1.65-3.39; p<0.0001). On the contrary, individuals who inherited a CTLA-4 CT60 A allele had less chance to develop GD (OR=0.42; 95%CI=0.30-0.61; p<0.0001). The inheritance of a polymorphic CTLA-4 –318 gene was more frequent in older patients (42.90±10.83 versus 38.84±11.81 years old, p=0.0105), in the ones with elevated serum TRAb levels (p=0.0229) and also in those submitted to higher therapeutic doses of radioiodine (p=0.0237) when compared with wild-type genotype. The CC genotype of PTPN22 also increased the risk (OR=2.11; 95%CI=1.16-3.83; p=0.03496), whereas PTPN22 T allele protected against GD (OR=0,47; 95%CI=0,26-0,86; p=0,03496). The inheritance of a TSHR AA genotype for rs179247 increased the susceptibility for GD (OR=2.821; 95%IC=1.595-4.990; p=0.0004), and the TSHR GG genotype for rs12885526 increased the risk for Graves' ophthalmopathy (OR=2.940; 95%CI=1.320-6.548; p=0.0083). In conclusion, we demonstrated that CTLA-4, PTPN22 and TSHR polymorphisms are associated not only to the susceptibility, but also to clinical features and to the outcome of GD patients.
Nothing to Disclose: NEB, AGR, RBS, JHR, LSW