Association Between Promoter Polymorphisms of IL-1B, IL-4 and IL-6 Genes and a Viral Load Infected Women with Human Papillomavirus

Abstract

Background: The purpose of this study was to investigate the association between IL-4 -589C>T, IL-6 -174G>C, IL-1β -31T>C and IL-1β -511C>T genes polymorphism with high concentrations of human papillomavirus (HPV), and the influence of gene-gene interactions on persistent human papillomavirus infection.

Methods: In this study, 101 infected women with high HPV viral load and 93 healthy women were involved in a case-control study. Genotyping of SNPs for IL-4 -589C>T, IL-6 -174G>C, IL-1β -31T>C and IL-1β -511C>T genes was carried out by allele-specific PCR. Quantitative analysis of HPV-DNA was performed by Amplisens HPV HCR genotype-titer software. Gene-gene interactions were analyzed using multifactor dimensionality reduction (MDR) algorithm. Haplotype interactions were analyzed by HaploView 4.2 tool.

Results: The study of single individual SNPs in promoters of IL-4 -589C>T, IL-6 -174G>C and IL-1β -31T>C genes did not reveal statistically significant difference in genotypes and allele frequencies among women with high HPV viral load and control group. The frequency of -511T allele and TT genotype of the IL-1β gene in case group was significantly higher than the one in control group (OR=1.71, p=0.012 and OR=2.02, p=0.046, respectively). Haplotype analysis revealed that -511C/-31T haplotype for IL-1β gene is significantly less common among women with high HPV viral load (p=0.018).

Conclusion: The haplotype -511C/-31T for IL-1β gene is associated with a protective effect against increasing HPV viral load. The frequencies of -511T allele and -511TT genotype of the IL-1β -511C>T were significantly higher among women with HPV in comparison to control group.

Keywords: Cytokines; Human papillomavirus (HPV); Inflammation; Polymorphism; Viral load.

Figure 4.

Interaction analysis among polymorphic variants of IL-1β -31T> C, IL-1β -511C> T, IL4 -589C> T and IL6 -174G> C for women with high HPV viral load. The informational value of each marker is presented on vertices; the informational value of the interaction for a pair of loci is presented on the edges

Figure 1.

Real-time processing of human papillomavirus amplification products on a RotorGene

Figure 2.

Excel table with quantitative HPV load

Figure 3.

Electrophoresis for amplification products of -511C>T IL-1β gene. Wells 1 and 2 are negative controls. The wells with odd numbers contain amplification products after PCR with primers of the normal allele. In contrast, the wells with even numbers contain amplification products after PCR with primers of the mutant allele. The wells 3-4, 5-6, 7-8, 9-10 contain amplification products for one DNA sample. The homozygous genotype IL-1β -511CC is observed in wells 9 and 10. The homozygous genotype IL-1β -511TT is observed in wells 3-4 and 5-6 while the heterozygous genotype IL-1β -511CT is detected in wells 7 and 8