title: Evidence for an epistatic effect between TP53 R72P and MDM2 T309G SNPs in HIV infection: a cross-sectional study in women from South Brazil.
abstract: OBJECTIVE
  To investigate the associations of TP53 R72P and MDM2 T309G SNPs with HPV infection status, HPV oncogenic risk and HIV infection status.
  
  
  METHODS
  Cross-sectional study combining two groups (150 HIV-negative and 100 HIV-positive) of women.
  
  
  METHODS
  Data was collected using a closed questionnaire. DNA was extracted from cervical samples. HPV infection status was determined by nested-PCR, and HPV oncogenic risk group by Sanger sequencing. Both SNPS were genotyped by PCR-RFLP. Crude and adjusted associations involving each exposure (R72P and T309G SNPs, as well as 13 models of epistasis) and each outcome (HPV status, HPV oncogenic risk group and HIV infection) were assessed using logistic regression.
  
  
  RESULTS
  R72P SNP was protectively associated with HPV status (overdominant model), as well as T309G SNP with HPV oncogenic risk (strongest in the overdominant model). No epistatic model was associated with HPV status, but a dominant (R72P over T309G) protective epistatic effect was observed for HPV oncogenic risk. HIV status was strongly associated (risk factor) with different epistatic models, especially in models based on a visual inspection of the results. Moreover, HIV status was evidenced to be an effect mediator of the associations involving HPV oncogenic risk.
  
  
  CONCLUSIONS
  We found evidence for a role of R72P and T309G SNPs in HPV status and HPV oncogenic risk (respectively), and strong associations were found for an epistatic effect in HIV status. Prospective studies in larger samples are warranted to validate our findings, which point to a novel role of these SNPs in HIV infection.
authors.affiliation: Postgraduate Program in Epidemiology, Department of Social Medicine, Faculty of Medicine, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil ; Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Fernando Pires
authors.initials: FP
authors.lastname: Hartwig
authors.affiliation: Postgraduate Program in Biotechnology, Technology Development Center (Biotechnology Unit), Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil ; Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Ludmila Gonçalves
authors.initials: LG
authors.lastname: Entiauspe
authors.affiliation: Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Emily Montosa
authors.initials: EM
authors.lastname: Nunes
authors.affiliation: Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Fernanda Martins
authors.initials: FM
authors.lastname: Rodrigues
authors.affiliation: Postgraduate Program in Biotechnology, Technology Development Center (Biotechnology Unit), Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil ; Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Collares
authors.affiliation: Postgraduate Program in Biotechnology, Technology Development Center (Biotechnology Unit), Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil ; Molecular and Cellular Oncology Research Group, Biotechnology Unit, Technology Development Center, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Fabiana Kömmling
authors.initials: FK
authors.lastname: Seixas
authors.affiliation: Postgraduate Program in Epidemiology, Department of Social Medicine, Faculty of Medicine, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil ; Maternal and Child Department, Faculty of Medicine, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Mariângela Freitas
authors.initials: MF
authors.lastname: da Silveira
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2