title: Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma.
abstract: BACKGROUND
  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.
  
  
  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%, respectively, and was significantly higher when in the presence of allele T (p = 0.002).
  
  
  CONCLUSIONS
  The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.
authors.affiliation: Graduate Program in Medicine: Hepatology, Fundação Universidade Federal de Ciências da Saúde de Porto Alegre, RS, Brazil. vabaldissera@gmail.com
authors.forename: Vanessa Dido
authors.initials: VD
authors.lastname: Baldissera
authors.forename: Angelo Alves
authors.initials: AA
authors.lastname: de Mattos
authors.forename: Gabriela Perdomo
authors.initials: GP
authors.lastname: Coral
authors.forename: Fernanda Branco
authors.initials: FB
authors.lastname: de Araujo
authors.forename: Cláudio Augusto
authors.initials: CA
authors.lastname: Marroni
authors.forename: Ajácio Bandeira
authors.initials: AB
authors.lastname: de Mello Brandão
authors.forename: Paulo Roberto
authors.initials: PR
authors.lastname: Ott Fontes
authors.forename: Carlos Thadeu
authors.initials: CT
authors.lastname: Schmidt Cerski
authors.forename: Antonio Atalibio
authors.initials: AA
authors.lastname: Hartmann
authors.forename: Nélson Alexandre
authors.initials: NA
authors.lastname: Kretzmann Filho
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor