Open Access Research article

The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

Kirvis Torres-Poveda1, Ana I Burguete-García1, Miguel Cruz2, Gabriela A Martínez-Nava1, Margarita Bahena-Román1, Esmeralda Ortíz-Flores1, Abrahan Ramírez-González1, Guillermina López-Estrada3, Karina Delgado-Romero4 and Vicente Madrid-Marina1*

Author Affiliations

1 Dirección de Infecciones Crónicas y Cáncer. Centro de Investigación sobre Enfermedades Infecciosas (CISEI), Instituto Nacional de Salud Pública, Av. Universidad 655, Santa María Ahuacatitlán, Cuernavaca, C.P.62100, Cuernavaca, México

2 Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades, Centro Médico Siglo XXI, IMSS, Mexico, DF, Mexico

3 Private Health Center for Gynecology, Cuernavaca, Morelos, Mexico

4 Centro de Atención para la Salud de la Mujer (CAPASAM). (Center for Women’s Health), Health Services of the State of Morelos, Cuernavaca, Mexico

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Infectious Agents and Cancer 2012, 7:32  doi:10.1186/1750-9378-7-32

Published: 14 November 2012

Abstract

Background

Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).

Methods

Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.

Results

No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.

Conclusions

The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.

Keywords:
IL-10 promoter polymorphisms; Squamous intraepithelial cervical lesions; IL-10 expression; Risk factors