title: 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.
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.
authors.affiliation: 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. vmarina@insp.mx.
authors.forename: Kirvis
authors.initials: K
authors.lastname: Torres-Poveda
authors.forename: Ana I
authors.initials: AI
authors.lastname: Burguete-García
authors.forename: Miguel
authors.initials: M
authors.lastname: Cruz
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Martínez-Nava
authors.forename: Margarita
authors.initials: M
authors.lastname: Bahena-Román
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Ortíz-Flores
authors.forename: Abrahan
authors.initials: A
authors.lastname: Ramírez-González
authors.forename: Guillermina
authors.initials: G
authors.lastname: López-Estrada
authors.forename: Karina
authors.initials: K
authors.lastname: Delgado-Romero
authors.forename: Vicente
authors.initials: V
authors.lastname: Madrid-Marina