Medical Microbiology and Immunology

, Volume 208, Issue 1, pp 49–58 | Cite as

Polymorphisms in the TGFB1 signal peptide influence human papillomavirus infection and development of cervical lesions

  • Kleber Paiva Trugilo
  • Guilherme Cesar Martelossi Cebinelli
  • Fernanda Costa Brandão Berti
  • Nádia Calvo Martins Okuyama
  • Fernando Cezar-dos-Santos
  • Michelle Mota Sena
  • Luis Fernando Lásaro Mangieri
  • Maria Angelica Ehara Watanabe
  • Karen Brajão de OliveiraEmail author
Original Investigation


The main purpose was to assess the effect of c.29C>T and c.74G>C polymorphisms in the TGFB1 signal peptide on HPV infection and development of cervical lesions. Cervical swabs and blood samples were obtained from 349 outpatient women, along with socio-demographic and sexual behavioral data. The study population was stratified by absence or presence of HPV DNA, as tested by PCR, as well as by lesion grade. TGFB1 signal peptide polymorphisms were genotyped using PCR-restriction fragment length polymorphism. HPV DNA was detected in 172 (49.3%) patients. c.74GC and the combined c.29CC+CT/c.74GC genotype were more frequent in infected patients (35.1 and 15.7%) than in uninfected women (6.2 and 14.7%). Accordingly, these genotypes were associated with a higher risk of HPV infection, with odds ratio and 95% confidence interval of 2.81 and 1.35–5.86 (P = 0.004) for c.74GC and 3.14 and 1.42–6.94 (P = 0.004) for the combined genotype, respectively. High-grade lesions were also 2.48 times more likely to occur in c.29CC patients than in c.29TT patients, with a 95% confidence interval of 1.01–6.08 (P = 0.047). The data demonstrate that c.74G>C and c.29C>T polymorphisms are significantly associated with risk of HPV infection and high-grade squamous intraepithelial lesions, respectively. Thus, TGFB1 signal peptide polymorphisms are potential susceptibility markers.


TGFB1 combined genotype Susceptibility markers rs1800470 rs1800471 



The authors thank the volunteers who participated in the study, the Intermunicipal Consortium of Health of the Middle Paranapanema, the University Hospital and Clinic Center of State University of Londrina, the Municipal Health Department of Londrina, Londrina—PR, Brazil, and Londrina State University Coordination for Postgraduation.


This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (470137/2013-4), Fundação Araucária—Programa Pesquisa para o SUS (34935.406.36850.19112012). This work received fellowship support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and financial support for language editing from FAEPE/UEL-PUBLIC 2016.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kleber Paiva Trugilo
    • 1
  • Guilherme Cesar Martelossi Cebinelli
    • 1
  • Fernanda Costa Brandão Berti
    • 1
  • Nádia Calvo Martins Okuyama
    • 1
  • Fernando Cezar-dos-Santos
    • 1
  • Michelle Mota Sena
    • 1
  • Luis Fernando Lásaro Mangieri
    • 2
  • Maria Angelica Ehara Watanabe
    • 1
  • Karen Brajão de Oliveira
    • 1
    Email author
  1. 1.Department of Pathological Science, Biological Science CenterState University of LondrinaLondrinaBrazil
  2. 2.Department of Gynecology and Obstetrics, Health Science CenterState University of LondrinaLondrinaBrazil

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