Haplotype Structures and Protein Levels of TGFB1 in HPV Infection and Cervical Lesion: A Case-Control Study
Kleber Paiva Trugilo,
Guilherme Cesar Martelossi Cebinelli,
Érica Romão Pereira,
Nádia Calvo Martins Okuyama,
Fernando Cezar-dos-Santos,
Eliza Pizarro Castilha,
Tamires Flauzino,
Valéria Bumiller-Bini Hoch,
Maria Angelica Ehara Watanabe,
Roberta Losi Guembarovski,
Karen Brajão de Oliveira
Affiliations
Kleber Paiva Trugilo
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Guilherme Cesar Martelossi Cebinelli
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Érica Romão Pereira
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Nádia Calvo Martins Okuyama
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Fernando Cezar-dos-Santos
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Eliza Pizarro Castilha
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Tamires Flauzino
Laboratory of Research in Applied Immunology, State University of Londrina, Londrina 86057-970, PR, Brazil
Valéria Bumiller-Bini Hoch
Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba 80060-000, PR, Brazil
Maria Angelica Ehara Watanabe
Laboratory of Studies and Applications of DNA Polymorphisms and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
Roberta Losi Guembarovski
Laboratory of Mutagenesis and Oncogenetics, Department of Biological Sciences, State University of Londrina, Londrina 86057-970, PR, Brazil
Karen Brajão de Oliveira
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina 86057-970, PR, Brazil
This study aimed to verify the role of TGFB1 variants (c.–1638G>A, c.–1347C>T, c.29C>T, and c.74G>C) in HPV infection susceptibility and cervical lesions development, and their impact on TGFB1 cervical and plasma levels. TGFB1 genotypes were assessed with PCR-RFLP and haplotypes were inferred for 190 HPV-uninfected and 161 HPV-infected women. TGFB1 levels were determined with immunofluorimetric assay. Case-control analyses were performed with logistic regression adjusted for possible confounders. Women carrying –1347TT or –1347CT+TT as well as those with 29CT, 29CC, or 29CT+CC were more likely to have HPV than –1347CC and 29TT carriers, respectively. Regarding haplotypes, the most frequent were *4 (GCTG) and *3 (GTCG). Women *4/*4 were less likely to have HPV than those with no *4 copy. Comparing the inheritance of *3 and *4, carriers of *3/*4 or *3/*3 were more susceptible to HPV than *4/*4. The TGFB1 plasma and cervical levels were higher in the infected patients. Plasma levels were also higher in infected women with low-grade lesions. HPV-infected patients carrying *3/Other and *3/Other+*3/*3 presented lower TGFB1 plasma levels than those with no copy of *3. TGFB1 variants could contribute to the comprehension of the TGFB1 role in HPV-caused cervical disease.
