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      Distribución del polimorfismo del codón 72 del gen p53 en lesiones de cuello uterino

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          Abstract

          Objetivo: Determinar la distribución del polimorfismo del codón 72 del gen p53 en pacientes que presentan lesiones cervicales asociadas a infección por VPH. Métodos: Estudio descriptivo de corte transversal donde se procesaron 118 muestras del área genital femenina, de 59 mujeres sanas (controles) y 59 con lesiones cervicales NICI-NICII-NICIII y Ca in situ (casos), para la extracción y purificación del ADN. Se amplificó el exón 4 del gen p53, para la genotipificación del codón 72 mediante la técnica PCR-SSCP. Ambiente: Facultad de Ciencias, Laboratorio de Biología y Medicina Experimental LABIOMEX, Universidad de Los Andes. Mérida, Estado Mérida, Venezuela. Resultados: La PCR-SSCP permitió determinar la frecuencia de los genotipos homocigotos arginina (Arg/Arg), prolina (Pro/Pro) y heterocigoto prolina/arginina (Pro/Arg). Para los casos el genotipo Arg/Arg tuvo una frecuencia de 32,20 % y para los controles de 50,85 %. El genotipo Pro/Pro se encontró en 5,09 % de los casos y 11,86 % para los controles. El genotipo Pro/Arg tuvo una distribución de 62,71 % para los casos y 37,29 % para los controles. Conclusión: En este estudio no se encontró una relación estadísticamente significativa entre la presencia del genotipo Arg/Arg y el desarrollo de lesiones cervicales.

          Translated abstract

          Objective: To determine the distribution of the polymorphism of the codon 72 of the gene p53 in patients that present cervical lesions associated to infection by VPH. Method: Descriptive and transversal study through assessment of 118 samples of the genital feminine area were processed, of 59 healthy (control) women and 59 with cervical lesions NICI-NICII-NICIII and Ca in situ (cases), for the extraction and purification of the DNA. The exon 4 of the gene p53 was amplified, for the genotipification of the codon 72 by means of technical PCR-SSCP. Setting: Facultad de Ciencias, Laboratorio de Biologia y Medicina Experimental LABIOMEX, Universidad de Los Andes. Merida, Estado Merida, Venezuela. Results: PCR-SSCP allowed determining the frequency of the homozygotes genotypes arginine (Arg/Arg), proline (Pro/Pro) and heterozygotes proline /arginine (Pro/Arg). For the cases the genotype Arg / Arg had a frequency of 32.20 % and for the controls of 50.85 %. The genotype Pro/Pro was in 5.09 % of the cases and 11.86 % for the controls. The genotype Pro/Arg had a distribution of 62.71 % for the cases and 37.29 % for the controls. Conclusion: In this investigation there was not a statistically significant relationship among the presence of the genotype Arg/Arg and the development of cervical lesions.

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          Most cited references41

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          Molecular Cloning : A Laboratory Manual

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            Role of a p53 polymorphism in the development of human papillomavirus-associated cancer.

            The E6 oncoprotein derived from tumour-associated human papillomaviruses (HPVs) binds to and induces the degradation of the cellular tumour-suppressor protein p53. A common polymorphism that occurs in the p53 amino-acid sequence results in the presence of either a proline or an arginine at position 72. The effect of this polymorphism on the susceptibility of p53 to E6-mediated degradation has been investigated and the arginine form of p53 was found to be significantly more susceptible than the proline form. Moreover, allelic analysis of patients with HPV-associated tumours revealed a striking overrepresentation of homozygous arginine-72 p53 compared with the normal population, which indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes. The arginine-encoding allele therefore represents a significant risk factor in the development of HPV-associated cancers.
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              Two polymorphic variants of wild-type p53 differ biochemically and biologically.

              The wild-type p53 protein exhibits a common polymorphism at amino acid 72, resulting in either a proline residue (p53Pro) or an arginine residue (p53Arg) at this position. Despite the difference that this change makes in the primary structure of the protein resulting in a difference in migration during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no differences in the biochemical or biological characteristics of these wild-type p53 variants have been reported. We have recently shown that p53Arg is significantly more susceptible than p53Pro to the degradation induced by human papillomavirus (HPV) E6 protein. Moreover, this may result in an increased susceptibility to HPV-induced tumors in homozygous p53Arg individuals. In further investigating the characteristics of these p53 variants, we now show that both forms are morphologically wild type and do not differ in their ability to bind to DNA in a sequence-specific manner. However, there are a number of differences between the p53 variants in their abilities to bind components of the transcriptional machinery, to activate transcription, to induce apoptosis, and to repress the transformation of primary cells. These observations may have implications for the development of cancers which harbor wild-type p53 sequences and possibly for the ability of such tumors to respond to therapy, depending on their p53 genotype.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                og
                Revista de Obstetricia y Ginecología de Venezuela
                Rev Obstet Ginecol Venez
                Sociedad de Obstetricia y Ginecología de Venezuela (Caracas )
                0048-7732
                March 2010
                : 70
                : 1
                : 31-36
                Affiliations
                [1 ] Universidad de Los Andes Venezuela
                Article
                S0048-77322010000100006
                8c18ca3d-04e3-472d-9159-e3a0cf9e69a8

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Venezuela

                Self URI (journal page): http://www.scielo.org.ve/scielo.php?script=sci_serial&pid=0048-7732&lng=en
                Categories
                OBSTETRICS & GYNECOLOGY

                Obstetrics & Gynecology
                HPV,P53,Codon 72,PCR-SSCP,VPH,Codón 72
                Obstetrics & Gynecology
                HPV, P53, Codon 72, PCR-SSCP, VPH, Codón 72

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