Evauation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma



Título del documento: Evauation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma
Revista: Annals of hepatology
Base de datos: PERIÓDICA
Número de sistema: 000417652
ISSN: 1665-2681
Autors: 1
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Institucions: 1Fundacao Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, Rio Grande do Sul. Brasil
2Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul. Brasil
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Període: Nov-Dic
Volum: 11
Número: 6
Paginació: 899-906
País: México
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Aplicado, analítico
Resumen en inglés Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. Objective. To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. Material and methods. A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. Results. Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%
Disciplines Medicina
Paraules clau: Gastroenterología,
Oncología,
Genética,
Hígado,
Tumores,
Polimorfismos de nucleótido único (SNPs),
Resistencia multifármacos,
Glicoproteína P,
MDR1
Keyword: Gastroenterology,
Oncology,
Genetics,
Liver,
Tumors,
Single nucleotide polymorphism (SNPs),
Multidrug resistance,
P-glycoprotein,
MDRI
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