TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression
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Natália Pereira da Rocha1, Elyzabeth Avvad-Portari2, Fábio Russomano3, Eric Henrique Roma1, Amanda Chaves Pinto4, Evandro Klumb5, Jacyara Macedo4, Ana Teresa Gomes Fernandes1 and Maria da Glória Bonecini-Almeida1
1Laboratory of Immunology and Immunogenetics in Infectious Diseases, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
2Department of Pathologic Anatomy, Fernandes Figueira Woman, Child and Adolescent National Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
3Women´s Health Care Area, Fernandes Figueira Woman, Child and Adolescent National Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
4Department of Biochemistry, State University of Rio de Janeiro, Rio de Janeiro, Brazil
5Department of Rheumatology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
Maria da Glória Bonecini-Almeida, email: email@example.com
Keywords: HPV; cervical lesions; in situ TNFR1; TNFR1 SNPs
Received: August 15, 2018 Accepted: January 14, 2019 Published: January 29, 2019
TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 and rs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p < 0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression.
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