Abstract
Graves\ disease (GD) is a multifactorial condition presumably provoked by environmental factors, including viruses, whose interactions with the immune system have been proposed to trigger the disease. HHV are ubiquitous, tissue tropism widespread, and have been found in the thyroid that can be a reservoir of latent HHV. TP53 gene plays a critical role in cell cycle control, facilitating DNA repair activities and protecting against DNA damages.
We recently demonstrated an increased risk for HHV6 infection in individuals that inherited a polymorphism that diminishes p53 apoptotic activity. Hence, we aimed to study the relationship between HHV6 and HHV7 infection, p53 apoptotic ability as represented by 72p53 polymorphisms and GD susceptibility. Sixty GD patients were paired to 60 controls with respect to gender, age, color and environmental exposure. We used nested-primers to identify HHV6 and HHV7 and PCR-RFLP to sort out 72p53 polymorphisms. Patients were treated according to a same protocol. Both viruses infection increased the risk for GD (OR=2.507;95%CI=1.256-5.004; p=0.0125), especially HHV7 that was more frequent among GD (64.64%) than in controls (38.73%) (p=0.0006) increasing the risk to develop GD significantly (OR=2.892;95%CI=2.054-4.072;p<0.0001).
Patients 72TP53 Pro/Pro variants had more than 5 times more chance to develop GD (OR=5.196;95%CI=2.112-12.783;p><0.0001) and almost three times more chance to be infected by HHV7 (OR=2.835;95%CI=1.100-7.310;p=0.0275). We were not able to find any relationship between viral infection and patients clinical features, including ophthalmopathy, or their outcome. We suggest that both HHV infections, especially HHV7, increase the susceptibility to GD and this may be related to a deficient TP53 apoptotic activity.