title: A Functional Variant at the miR-214 Binding Site in the Methylenetetrahydrofolatereductase Gene Alters Susceptibility to Gastric Cancer in a Chinese Han Population.
abstract: OBJECTIVE
  Single nucleotide polymorphisms in miRNA binding sites, which are located in mRNA 3' untranslated regions (3'-UTRs), were recently found to influence microRNA-target interactions. Specifically, such polymorphisms can modulatebinding affinity or create or destroy miRNA-binding sites; such variants have also been found to be associated with cancer risk. In this study, we explored the effect of a functional variant at the miR-214 binding site in the methylenetetrahydrofolate reductase gene (rs114673809) on gastric cancer (GC) risk in a hospital-based case-control study in a Chinese Han population.
  
  
  RESULTS
  We genotyped the rs114673809 polymorphism in 345 gastric cancer patients and 376 cancer-free controls using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The functions of rs114673809 were investigated using a luciferase activity assay and validated by immunoblotting. We found that participants carrying the rs114673809 AA genotype or A allele had a significantly increased risk of gastric cancer (OR = 1.667, 95% CI = 1.044-2.660, P = 0.034; OR = 1.261, 95% CI = 1.017-1.563, P = 0.037, respectively) compared to those carrying the GG genotype and G allele. In addition, rs114673809 modified the binding of hsa-miR-214 to MTHFR as well as MTHFR protein levels in gastric cancer patients.
  
  
  CONCLUSIONS
  Our data suggested that rs114673809, which is located at the miR-214 binding site in the 3'-UTR of MTHFR, may play an important role in the development of gastric cancer in a Chinese Han population.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Qin
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Yangchen
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001665:Binding Sites; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D042965:Methylenetetrahydrofolate Reductase (NADPH2)