title: Genetic Variation in the ABCB1 Gene May Lead to mRNA Level Chabge: Application to Gastric Cancer Cases.
abstract: BACKGROUND
  One of the major mechanisms for drug resistance is associated with altered anticancer drug transport, mediated by the human-adenosine triphosphate binding cassette (ABC) transporter superfamily proteins. The overexpression of adenosine triphosphate binding cassette, sub-family B, member 1 (ABCB1) by multidrug-resistant cancer cells is a serious impediment to chemotherapy. In our study we have studied the possibility that structural single-nucleotide polymorphisms (SNP) are the mechanism of ABCB1 overexpression.
  
  
  METHODS
  A total of 101 gastric cancer multidrug resistant cases and 100 controls were genotyped with sequence-specific primed PCR (SSP-PCR). Gene expression was evaluated for 70 multidrug resistant cases and 54 controls by real time PCR. The correlation between the two groups was based on secondary structures of RNA predicted by bioinformatics tool.
  
  
  RESULTS
  The results of genotyping showed that among 3 studied SNPs, rs28381943 and rs2032586 had significant differences between patient and control groups but there were no differences in the two groups for C3435T. The results of real time PCR showed over-expression of ABCB1 when we compared our data with each of the genotypes in average mode. Prediction of secondary structures in the existence of 2 related SNPs (rs28381943 and rs2032586) showed that the amount of ΔG for original mRNA is higher than the amount of ΔG for the two mentioned SNPs.
  
  
  CONCLUSIONS
  We have observed that 2 of our studied SNPs (rs283821943 and rs2032586) may elevate the expression of ABCB1 gene, through increase in mRNA stability, while this was not the case for C3435T.
authors.affiliation: Medical Cellular and Molecular Research Center Talghani Children Hospital of Golestan University of Medical Sciences, Bolv Janbazan, Iran E-mail : Shahbazimajid@yahoo.co.uk.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mansoori
authors.forename: Masoud
authors.initials: M
authors.lastname: Golalipour
authors.forename: Shahriar
authors.initials: S
authors.lastname: Alizadeh
authors.forename: Ataollah
authors.initials: A
authors.lastname: Jahangirerad
authors.forename: Seyed Reza
authors.initials: SR
authors.lastname: Khandozi
authors.forename: Habibollah
authors.initials: H
authors.lastname: Fakharai
authors.forename: Majid
authors.initials: M
authors.lastname: Shahbazi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D005472:Fluorouracil