The Association of the Immune Response Genes to Human Papillomavirus-Related Cervical Disease in a Brazilian Population

Abstract

The genetic variability of the host contributes to the risk of human papillomavirus (HPV)-related cervical disease. Immune response genes to HPV must be investigated to define patients with the highest risk of developing malignant disease. The aim of this study was to investigate the association of polymorphic immune response genes, namelyKIR, HLA class I and II, and single-nucleotide polymorphisms (SNPs) of cytokines with HPV-related cervical disease. We selected 79 non-related, admixed Brazilian women from the state of Paraná, southern region of Brazil, who were infected with high carcinogenic risk HPV and present cervical intraepithelial neoplasia grade 3 (CIN3), and 150 HPV-negative women from the same region matched for ethnicity.KIRgenes were genotyped using an in-house PCR-SSP. HLA alleles were typed using a reverse sequence-specific oligonucleotide technique. SNPs ofTNF −308G>A, IL6 −174G>C, IFNG +874T>A, TGFB1 +869T>C +915G>C,andIL10 −592C>A −819C>T −1082G>Awere evaluated using PCR-SSP. TheKIRgenes were not associated with HPV, although some pairs of i(inhibitory)KIR-ligands occurred more frequently in patients, supporting a role for NK in detrimental chronic inflammatory and carcinogenesis. Some HLA haplotypes were associated with HPV. The associations ofINFGandIL10SNPs potentially reflect impaired or invalid responses in advanced lesions.