RESUMEN
ABSTRACT Host immunogenetic setting is involved in the regulation of human papillomavirus (HPV) infection and development of condyloma acuminatum (CA). We investigated the correlation of two common single nucleotide polymorphisms (SNPs) (−607C/A and −137G/C) of IL-18 with the susceptibility of CA in a large Chinese cohort. Out of 408 CA patients analyzed, 300 had HPV infection transmitted through sexual contact (SC) and 108 through non-sexual contact (NSC). In addition, 360 healthy volunteers were enrolled as controls. SNPs at positions −607C/A and −137G/C in IL-18 promoter were analyzed. Comparing CA patients to healthy controls, no dominant relevance was found between the IL-18 promoter −607 C/A or −137G/C polymorphisms and the CA disease either identified genotypically (p > 0.05) or by allelically (p > 0.05). However, the IL-18 promoter −137G/C polymorphism genotype and allele frequencies in the NSC CA group, but not between in the SC group, were significantly higher than in the controls. There was no dominant relevance between IL-18-607C/A polymorphism genotype and allele frequencies among SC, NSC CA patients, and controls. Our study demonstrates that polymorphism −137G/C in IL-18 promoter is significantly correlated with risk of CA in NSC patients.
Asunto(s)
Humanos , Masculino , Femenino , Condiloma Acuminado/genética , Interleucina-18/genética , Polimorfismo de Nucleótido Simple/genética , Infecciones por Papillomavirus/complicaciones , Polimorfismo Genético , Condiloma Acuminado/virología , China , Estudios de Cohortes , Regiones Promotoras Genéticas , Predisposición Genética a la Enfermedad , Infecciones por Papillomavirus/transmisión , Pueblo Asiatico/genética , Alelos , GenotipoRESUMEN
Los papilomavirus humano (PVH) infectan epitelios estratificados queratinizados con una alta especificidad y están asociados con la aparición y persistencia de neoplasias benignas y malignas. Los elementos que dirigen la expresión genética de estos virus se localizan en una región no codificadora conocida como región larga de control (RLC). Al inicio del ciclo viral, una combinación particular de factores celulares que interactúan con la RLC promueven la transcripción temprana de los oncogenes virales E6 y E7. Estos favorecen la división celular interrumpiendo los mecanismos regulatorios celulares: E6 se une a la proteína supresora de tumor p35 y E7 se une a p105RB. La continuidad en la transcripción temprana conlleva al aumento gradual de las proteínas virales E1 y E2. La proteína E2 impide la transcripción temprana y confiere especificidad de unión a E1, la cual promueve la replicación viral. El cese paulatino de la transcripción de los oncogenes virales a través de la represión por E2, libre la regulación del crecimiento celular mediada por p53 y p105RB, permitiendo que la diferenciación celular progrese. Es entonces cuando el promotor tardío funciona para la producción de las proteínas de la cápside viral L1 y L2, permitiendo la maduración de viriones en los estratos superiores del epitelio. La disrupción del gen E2 durante un evento de integración del genoma viral, impide la progreción del ciclo vira y la entrada del programa de diferenciación de la célula epitelial, sosteniendo el estado transformado producido por E6 y E7
Human papillomavirus (HPV) specifically infect stratified epithelial cells, causing benign and malignant neoplasia. Several elements directing this virus' genetic expression are present in a non-coding region called LCR. HPV infection starts in the basal cells of stratified epithelia, where a particular combination of cellular factors interacting with the LCR starts the transcription of the viral E6 and E7 oncogenes. The E6 and E7 genes alter the cell cycle because they interact and inactivate tumor suppressor proteins: E6 binds and degrades protein p53 and E7 associates with p105RB. E1 and E2 are the next synthesized proteins. E2 blocks the early transcription and permits E1 specific binding to the viral origin of replication located within the lcr, initiating the viral genome replication. Following the course of viral infection, the E2-induced E6 and E7 down-regulation releases p53 and p105RB proteins, and the differentiation process can continue. Then, a putative late promoter can activate the capsid genes L1 and L2. At this step, mature virions can be detected in the upper layers of the epithelium. Disruption in E2 gene transcription is usually associated to genital malignant neoplasia. In the absence of E2, E6 and E7 remain constitutively expressed, sustaining the immortality of the infected cell and blocking the epithelial differentiation program.
Asunto(s)
Humanos , Masculino , Femenino , Oncogenes/genética , Papillomaviridae/genética , Condiloma Acuminado/genética , Regulación hacia Abajo , Genes Virales/genética , Neoplasias de los Genitales Femeninos/etiología , Neoplasias de los Genitales Masculinos/etiología , Regulación Viral de la Expresión Génica , Transcripción Genética/genéticaRESUMEN
Specimens from cervical dysplasias or carcinomas and genital condylomata acuminata were retrospectively analysed by in situ hybridization (ISH) with biotinylated DNA probes for human papillomavirus (HPV) types 6, 11, 16 and 18. In the control group no case was positive for HPV DNA. In mild/moderate dysplasias, 4 cases (14%) were positive for HPV 6 or 11 and 2 cases (7%), for HPV 16. In the severe dysplasia/in situ carcinoma group, 9 cases (31%) showed presence of DNA of HPV types 16 or 18. Six invasive carcinomas (20%) were positive for HPV type 16 or 18. Among condylomata acuminata, 22 cases (73%) were positive for HPV types 6 or 11. In all ISH-positive cases only one viral type was detected. No correlation between HPV DNA positivity and histological findings of HPV infection was observed. Although less sensitive than some other molecular biology techniques, in situ hybridization with biotinylated DNA probes proved to be simple and useful for detecting and typing HPV in samples routinely received for histopathological analysis