Genetic variant in CXCL12 gene raises susceptibility to HPV infection and squamous intraepithelial lesions development: a case-control study

J Biomed Sci. 2018 Sep 18;25(1):69. doi: 10.1186/s12929-018-0472-y.

Abstract

Background: Human papillomavirus (HPV) is the most common sexually transmitted virus in women worldwide. The persistence of the virus may cause warts that are considered benign lesions and low or high grade intraepithelial lesions (LSIL/HSIL). Immunological system plays an important role in the resolution of infections. In this context, we highlight the chemokines, which are important regulators in the development of viral infections and inflammation. Among which CXCL12 stands out, due to its pro-inflammatory features, acting as chemoattractant recruiting immune cells. Several polymorphisms were identified in CXCL12 gene including rs1801157 in the 3'-untranslated region, which is characterized by a substitution of a guanine for an adenine.

Methods: In this study, 195 women were classified as HPV non-infected and 169 as HPV-infected. HPV-DNA was detected by polymerase chain reaction (PCR) and the polymorphism was assessed in blood cells through restriction fragment length polymorphism analysis.

Results: HPV infection was more incident in women who had more than 4 sexual partners during lifetime (p = 0.007), among those who presented lower number of pregnancies (p = 0.017). HPV was more prevalent among allele A carriers confirmed by logistic regression analysis adjusted for several confounding factors [ORADJ = 4.985; CI95% (2.85-8.72), p < 0.001]. An association between allele A carriers and HSIL development (p = 0.003) was also observed.

Conclusions: In the present study, we demonstrated that CXCL12 rs1801157 is independently associated with HPV infection and exerts influence in HSIL development, suggesting it as a promising susceptibility biomarker for HPV infection and lesions development.

Keywords: CXCL12; Cervical lesion; HPV infection; rs1801157 polymorphism.

MeSH terms

  • Adult
  • Brazil / epidemiology
  • Case-Control Studies
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Disease Susceptibility / virology
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Humans
  • Incidence
  • Middle Aged
  • Papillomaviridae / physiology
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / epidemiology*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / virology
  • Prevalence
  • Squamous Intraepithelial Lesions of the Cervix / epidemiology*
  • Squamous Intraepithelial Lesions of the Cervix / genetics
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Young Adult

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12