H. Pylori CagA Induces Hypermethylation of Let-7 Promoter CpG Islands and Lymphomagenesis

141), and asymptomatic age-matched controls (n=202).Genotyping was performed on known tagging SNPs in highly conserved parts of the 5'regulatory region of the VDR gene.Radioactive gel shift assay was used to investigate GATA binding affinity.In 25 of the genotyped BE patients, VDR mRNA levels were determined in esophageal biopsies.Results: Dose-risk allele analysis showed that subjects carrying the 1633G/1453T haplotype were less susceptible to EE (OR 0.48; 95%CI 0.28-0.81),BE (OR 0.46; 95%CI 0.26-0.80),and EAC (OR 0.50; 95%CI 0.27-0.96).For BE, this observation was replicated in an independent cohort of 150 patients (OR 0.44; 95%CI 0.23-0.85).Super shift analysis showed that the 1453C→T mutation increased binding of the transcription factor GATA-1.Moreover, in BE patients carrying two GT-alleles VDR mRNA levels in esophageal biopsy samples were 3fold lower than in patients lacking .Conclusion: This study shows that GT-haplotype near the 1c region of the VDR gene is associated with a decreased susceptibility to EE, BE, and EAC.It causes an increase in GATA-1 binding to this regulatory region, thereby inhibiting transcription of the VDR gene.