The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion.

Autor:	Medeiros FS; Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., da Silva MC; Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., da Silva NCH; Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Gomes TT; Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Gomes RG; Laboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, Brazil., Paiva LA; Getúlio Vargas Hospital, Pernambuco Health Department, Recife, Brazil., Dos Santos Gomes FO; Laboratory of Ultrastructure, Department of Entomology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Peixoto CA; Laboratory of Ultrastructure, Department of Entomology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil., Rygaard MCV; Laboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, Brazil., Welkovic S; Integrated Health Center Amaury de Medeiros (CISAM), University of Pernambuco, Recife, Brazil., Menezes MLB; Integrated Health Center Amaury de Medeiros (CISAM), University of Pernambuco, Recife, Brazil., Donadi EA; Clinical Immunology Division, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil., Lucena-Silva N; Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.; Laboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2022 Dec 21; Vol. 12, pp. 979800. Date of Electronic Publication: 2022 Dec 21 (Print Publication: 2022).
DOI:	10.3389/fcimb.2022.979800
Abstrakt:	Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1 , and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Medeiros, Silva, Silva, Gomes, Gomes, Paiva, dos Santos Gomes, Peixoto, Rygaard, Welkovic, Menezes, Donadi and Lucena-Silva.)
Databáze:	MEDLINE
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