El gen TP53 codifica una proteína de 53 kDa con importante función reguladora en procesos celulares como la proliferación, muerte celular y preservación del material genético. Polimorfismos de este gen presentan una alta diversidad en la distribución de las frecuencias alélicas entre grupos étnicos y han sido relacionados con la susceptibilidad al cáncer. Utilizando la técnica de PCR-RFLP, se determinó las frecuencias alélicas de los polimorfismos intrón 3, intrón 6 y codón 72 en 58 estudiantes de la UNMSM (Lima) y 37 de la Universidad José Faustino Sánchez Carrión (Huacho). Se estimó la frecuencia génica y genotípica con el programa estadístico SPSS 11.5; y con el programa Arlequín versión 3.5, a través del índice de Nei, se estableció el grado de diferenciación genética entre ambas poblaciones al considerar el intrón 3, intrón 6 y codón 72, que resultó 1.793, 1.141 y 0.323 respectivamente. Ambas poblaciones están en equilibrio de Hardy-Weinberg (p>0.05) para los tres polimorfismos. En el codón 72, la frecuencia alélica para prolina resultó 30.1 % en la muestra de Lima y 29.7 % en la muestra de Huacho. La frecuencia del alelo para la arginina fue 69,8% para Lima y 70,2% en la de Huacho. Con relación al intrón 6, la frecuencia alélica para W en la de Lima fue 98.2 % y 81 % en la de Huacho. En contraste con el alelo M se obtuvo una frecuencia alélica de 1.7 % para la población estudiada de Lima y 18.9 % en la de Huacho. De otro lado, para el intrón 3 la frecuencia alélica W fue 94.6 % para Lima y 90 % para Huacho. En cambio la frecuencia alélica para M en los de Lima fue de 5.3 % y 10 % en los de Huacho. Se destaca el predominio del alelo Arg en el codón 72 para ambas poblaciones analizadas; así como el alelo W tanto en el intrón 6 como en el intrón 3. La comparación con las frecuencias alélicas de origen africano y asiático reveló diferencias estadísticamente significativas (p>0.001); sin embargo, se, observó una similitud con las poblaciones amerindias y caucásicas. PALABRAS CLAVE: gen TP53, polimorfismo Arg72Pro, intrón 6, intrón 3, poblaciones peruanas / --- The TP53 gene encodes a protein of 53 kDa with important regulatory role in cellular processes such as proliferation, cell death and preservation of genetic material. Polymorphisms of this gene have a high diversity in the distribution of allele frequencies between ethnic groups and have been linked to cancer susceptibility. By studying PCR-RFLP, was determined the allele frequencies of the polymorphisms, intron 3, intron 6 and codon 72 in 58 students of the University of UNMSM (Lima) and 37 at the University of Jose Faustino Sanchez Carrion. The Allelic and genotypic frequency was measured with the SPSS 11.5 statistical program; and with the Arlequin program ver. 3.5, through Nei index, was established the degree of genetic differentiation between the two populations by considering the intron 3, intron 6 and codon 72, which resulted in 1.793, 1.141 and 0.323 respectively. Both populations are in Hardy-Weinberg equilibrium (p> 0.05) for the three polymorphisms. At codon 72, the allele frequency for proline was 30.1 % in the sample of Lima and 29.7 % in the sample of Huacho. The allele frequency for arginine was 69.8 % for Lima and 70.2 % in Huacho. Regarding the intron 6, the allele frequency for W in Lima was 98.2 % and 81 % in Huacho. In contrast for the M was obtained an allelic frequency of 1.7 % for the studied population of Lima and 18.9 % in Huacho. On the other hand, for the intron 3 the allele frequency for W was 94.6 % for Lima and 90 % in Huacho. In contrast, the allele frequency for M in Lima was 5.3 % and 10 % in Huacho. The dominance of the Arg allele at codon 72 for both populations analyzed is highlighted; and the W allele both intron 6 and intron 3; and the W allele both intron 6 and intron 3. The comparison of allele frequencies of African and Asian descent revealed statistically significant differences (p <0.001); however, was observed a similarity with American and Caucasian populations. KEY WORDS: TP53 gene polymorphism Arg72Pro, intron 6, intron 3, Peruvian populations / Tesis

Made available in DSpace on 2014-08-20T13:32:46Z (GMT). No. of bitstreams: 1 Tese_Ludmila_Goncalves_Entiauspe.pdf: 1808464 bytes, checksum: 8834f78745c1e2d7f757d36d4797ef5c (MD5) Previous issue date: 2013-03-08 / Estimates show that approximately 80% of sexually active women will be infected by the Human Papillomavirus (HPV) in some point of their life course, and HPV DNA has been found in 99,7% of cervical cancer (CC) cases. Thus, several factors may contribute to CC development, including co-infections with Human Immunodeficiency Virus (HIV), as well as genetic factors, including TP53 and MDM2 polymorphisms. Some authors have associated CC development risk, among women infected with oncogenic HPV strains, with the Arg72Pro TP53 SNP. The MDM2 protein plays an important role in p53 protein regulation and, thus, a MDM2 SNP referred as SNP309 may also be implicated in CC risk in association with high-risk HPV genotypes. The present work aimed at determining the frequencies of HPV infection and identification of its genotypes, as well as the frequencies of the SNPs Arg72Pro and SNP309 and their associations with CC risk in female HIV-positive and negative populations in the city of Pelotas. It has been observed a prevalence of HPV infection of 30% among HIV-negative women, and 68% in the positive group. The HPV-16 genotype was the most prevalent in the HIV-negative group, and HPV-6 in the positive group. Among HPV-positive women, the TP53 Arg/Arg genotype was the most prevalent in both HIV groups, and the SNP309 TT genotype was the most prevalent in the HIV negative group, and the TG genotype in the positive group. These findings suggest that future investigations in larger populations are necessary and of interest to better understand the potential roles of these SNPs in HPV infected women. / Estimativas mostram que cerca de 80% das mulheres sexualmente ativas estarão infectadas pelo Vírus do Papiloma Humano (HPV) em algum momento de suas vidas, o que DNA-HPV tem sido encontrado em 99,7% dos casos de câncer cervical (CC). Assim, vários fatores podem contribuir para o desenvolvimento do CC, incluindo coinfecções como o vírus da Imunodeficiência Humana (HIV), bem como fatores genéticos, incluindo os polimorfismos nas proteínas p53 e MDM2. Alguns autores relacionam um maior risco ao desenvolvimento de CC em mulheres infectadas com genótipos oncogênicos do HPV e que apresentam polimorfismo do gene supressor de tumor TP53 (SNP Arg72Pro). A proteína MDM2 apresenta um papel importante na regulação da p53, e assim como o SNP Arg72Pro da p53, o SNP309 da MDM2 (substituição de T por G) também pode favorecer o desenvolvimento de CC quando associado a genótipos de HPV de alto risco. O presente trabalho objetivou conhecer o grau da extensão de infecção pelo HPV e identificação de seus genótipos, frequência do SNP Arg72Pro e MDM2 SNP309 e associação ao risco de CC, na população feminina HIV positiva e negativa residente em Pelotas. Foi observada uma prevalência de infecção por HPV em 30% no grupo HIV negativo e 68% no grupo HIV positivo. O genótipo de HPV mais prevalente no grupo HIV negativo foi o HPV-16, e HPV-6 no grupo HIV positivo. Nas HPV positivas, o genótipo Arg72Arg foi o mais prevalente em ambos os grupos, e o SNP309 TT para o grupo HIV negativo e TG para HIV positivo. Os resultados encontrados mostram que futuros estudos em populações maiores são necessários para um melhor entendimento destes SNPs em mulheres infectadas por HPV.

Made available in DSpace on 2014-08-20T13:32:57Z (GMT). No. of bitstreams: 1 tese_helena_strelow_thurow.pdf: 807973 bytes, checksum: 9ce5f5a742c1cda1d087be4eaaf27eae (MD5) Previous issue date: 2011-07-15 / A proteína p53,codificada pelo gene TP53, vem sendo estudada há mais de 30 anos e já foi denominada de "guardiã do genoma.