DEFB1 polymorphisms are involved in susceptibility to human papillomavirus infection in Brazilian gynaecological patients.

Ludovica Segat,Ronald Rodrigues Moura,Luisa Zupin,Bárbara Simas Chagas,Sergio Crovella,Antonio Victor Campos Coelho,Antonio Carlos De Freitas

doi:10.1590/0074-0276140220

Abstract

The human beta defensin 1 (hBD-1) antimicrobial peptide is a member of the innate immune system known to act in the first line of defence against microorganisms, including viruses such as human papillomavirus (HPV). In this study, five functional polymorphisms (namely g-52G>A, g-44C>G and g-20G>A in the 5’UTR and c.*5G>A and c.*87A>G in the 3’UTR) in the DEFB1 gene encoding for hBD-1 were analysed to investigate the possible involvement of these genetic variants in susceptibility to HPV infection and in the development of HPV-associated lesions in a population of Brazilian women. The DEFB1 g-52G>A and c.*5G>A single-nucleotide polymorphisms (SNPs) and the GCAAA haplotype showed associations with HPV-negative status; in particular, the c.*5G>A SNP was significantly associated after multiple test corrections. These findings suggest a possible role for the constitutively expressed beta defensin-1 peptide as a natural defence against HPV in the genital tract mucosa.

Highlights

Antimicrobial peptides and proteins (AMPs) are abundant and widely distributed molecules that play important roles in host defence as part of the innate immune system
The five DEFB1 gene polymorphisms were in Hardy-Weinberg equilibrium (HWE) in the group of human papillomavirus (HPV) patients and in the subgroups stratified according to the cervical lesions (HPV-positive patients without lesions, HPV-positive patients with cervical intraepithelial neoplasia (CIN) I, CIN II or CIN III lesions and HPV-positive patients with cervical cancer); among the healthy controls (HCs), the rs1800972 (g-44C>G) and rs1800971 (c.*87A>G) polymorphisms were in HWE, whereas the others were not (Table)
The 5’untranslated region (UTR) rs1799946 (g-52G>A) G/G genotype was more frequent among the healthy subjects than in the HPV patients and was associated with protection against HPV infection when compared to the G/A genotype

Summary

Introduction

Antimicrobial peptides and proteins (AMPs) are abundant and widely distributed molecules that play important roles in host defence as part of the innate immune system. We evaluated whether polymorphisms in the DEFB1 gene were associated with susceptibility to HPV infection and/or the development of genital tract lesions. DEFB1 polymorphisms allele, genotype and haplotype counts (and frequencies) in healthy controls (HC) and human papillomavirus (HPV) patients

Results

Conclusion