Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients.
In order to replicate their own genome in the host nucleus, herpesviruses have to overcome the barrier presented by p53 gene. Variants of codon 72 and codon 47 of exon four decrease the ability of p53 to induce apoptosis. In order to investigate the influence of this germline inheritance on the susceptibility to herpesvirus type 6 (HHV6) and 1 (HHV1) infection, we examined 78 renal transplant recipients and 151 controls. HHV6 infection was more frequent among the renal transplant patients (35.89%) than in the control population (11.25%) (P < 0.001). HHV1 infection rate was similar in renal transplant patients (7.28%) and controls (2.56%). HHV6-positive cases were more frequent among patients with codon 72 of p53 variants (60.71%) than among wild-type p53 patients (28.20%) (P = 0.001) despite the higher frequency of codon 72 of p53 wild-type variant in renal transplant patients compared with controls (64.1% vs. 36.4%; P < 0.001). The presence of a codon 72 of p53 germline variant genotype increased the risk for HHV6 infection more than five times (OR = 5.479; 95% CI = 1.992-15.069). Our data suggest that codon 72 of p53 polymorphism genotyping may be useful to screen for patients at higher risk for post-transplant infections hence identifying individuals that could benefit from preventive treatment.
Leite
Janaína L
JL
Department of Medicine, Laboratory of Cancer Molecular Genetics, School of Medicine, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Manfrinatto
Juliana A
JA
Mazzali
Marilda
M
Ward
Laura S
LS
D000328:Adult; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000453:epidemiology / Q000821:virology; D006561:Herpes Simplex / Q000453:epidemiology / Q000235:genetics*; D018259:Herpesvirus 1, Human; D015654:Herpesvirus 6, Human; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000453:epidemiology / Q000821:virology; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000453:epidemiology / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53