Article
Variation sites at the HLA-G 3' untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell
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MEDEIROS, F. S. et al. Variation Sites at the HLA-G 3’ Untranslated Region Confer Differential Susceptibility to HIV/HPV Co-Infection and Aneuploidy in Cervical Cell. PloS One, v. 13, n. 10, p. 1-14, 2018.
1932-6203
10.1371/journal.pone.0204679
Author
Medeiros, Fernanda Silva
Martins, Albert Eduardo Silva
Gomes, Renan Garcia
Oliveira, Sávio Augusto Vieira de
Welkovic, Stefan
Maruza, Magda
Menezes, Maria Luiza Bezerra
Ximenes, Ricardo Arraes de Alencar
Diniz, George Tadeu Nunes
Donadi, Eduardo Antônio
Lucena-Silva, Norma
Abstract
Post-transcriptional regulatory elements associated with transcript degradation or transcript instability have been described at the 3' untranslated region (3'UTR) of the HLA-G gene. Considering that HPV infection and aneuploidy, which causes gene instability, are associated with cervical cell malignancy, as well as the fact that HIV infection and HLA-G may modulate the immune response, the present study aimed to compare the frequencies of HLA-G 3'UTR polymorphic sites (14-base pair insertion/deletion, +3142C/G, and +3187A/G) between 226 HIV+ women co-infected (n = 82) or not with HPV (n = 144) and 138 healthy women. We also evaluated the relationship between those HLA-G 3'UTR variants and aneuploidy in cervical cells. HPV types and HLA-G polymorphisms were determined by PCR and sequencing of cervical samples DNA. Aneuploidy in cervical cell was measured by flow cytometry. The HLA-G 3'UTR 14-bp ins/del was not associated with either HIV nor HIV/HPV co-infection. The +3142G allele (p = 0.049) and +3142GG genotype (p = 0.047) were overrepresented in all HIV-infected women. On the other hand, the +3187G allele (p = 0.028) and the +3187GG genotype (p = 0.026) predominated among healthy women. The +3142G (p = 0.023) and +3187A (p = 0.003) alleles were associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co-infection. The diplotype formed by the combination of the +3142CX (CC or CG) and +3187AA genotype conferred the highest risk for aneuploidy in cervical cell induced by HPV. The HLA-G 3'UTR +3142 and +3187 variants conferred distinct susceptibility to HIV infection and aneuploidy.
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