Estudo dos herpesvirus humanos tipo 6 e tipo 1 e sua inter-relação com o gene TP53 em diferentes condições patologicas / Study of herpes viruses types 6 and type 1 and their relationship with TP53 gene in distinct pathological conditions

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Interactions between viruses, the immune system and detoxifying enzymes have been associated to the etiology of many conditions including cancer and various autoimmune diseases. We investigated the role of herpes viruses type 6 (HHV-6) and 1 (HHV-1) and the codon 72 (P72) and codon 47 (S47) variants of exon 4 of TP53, responsible for a diminished antiapoptotic activity of TP53, in the susceptibility to skin cancer and to Graves-Basedow Disease. We used PCR for virus detection, TP53 polymorphisms and GSTs, with restriction fragment length polymorphism analysis of some polymorphisms. When we studied 120 patient with skin lesions, compared with 41 controls we showed that the HHV-6 infection increases the risk of a patient to present basal cell carcinoma (OR=3.182; 95%CI: 1.125-8.997). The risk for HHV-1 infected patients was increased six times (OR=6.078;95%CI:1.365-27.061). We observed that this risk tended to be higher among immunocompromized patients. Were studied 78 kidney recipients compared with 151 controls. Was observed that HHV-6 infection was more frequent among kidney recipient patients (35.89%) than among the controls (11.25%) (F;p<0.0001). We also observed that HHV-6 positive patients appeared more frequently among kidney recipients patients that presented P72 variants (60.71%) than among those presenting the wild-type genotype Arg/Arg (22%) (F; p=0.001). To study the relationship between HHV-6 and autoimmune diseases, we analyzed 127 patients with Graves-Basedow Disease, observing that HHV-6 infected patients had a higher risk to developed this disease (OR=2.225;95%CI=1.197-4.135). The Pro/Pro of TP53 genotype was present in 11.8% of Graves-Basedow Disease patients (p<0.001), increasing significantly the risk to this disorder (OR=28.395; 95%CI=1.658-486.36). Therefore, our studies indicate that the presence of HHV-6 and HHV-1 increase the risk to skin cancer, suggesting that this virus can play a role in the susceptibility to skin malignancies; the germline inheritance of P72 increases the risk to HHV-6 infection and there is a tendency to a higher risk of Graves-Basedow Disease development in patients that have both an HHV-6 infection and the proline allele of codon 72 of TP53

ASSUNTO(S)

herpesviruses p53 genes p53 imunossupressão graves disease skin genes doença de graves pele - cancer herpesvirus immunosuppression

ACESSO AO ARTIGO

Documentos Relacionados