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

Abstract

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