title: Relationships among MTHFR a1298c gene polymorphisms and methylation status of Dact1 gene in transitional cell carcinomas.
abstract: OBJECTIVE
  The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population.
  
  
  METHODS
  Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed.
  
  
  RESULTS
  aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AAμAC genotype (P<0.05).
  
  
  CONCLUSIONS
  MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.
authors.affiliation: Department of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Cheng
authors.forename: Meng
authors.initials: M
authors.lastname: Lu
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Mao
authors.forename: Jun-Qi
authors.initials: JQ
authors.lastname: Wang
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.forename: Ru-Min
authors.initials: RM
authors.lastname: Wen
authors.forename: Jia-Cun
authors.initials: JC
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491683:DACT1 protein, human; D009687:Nuclear Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)