Premium
Correlation between global genome methylation and mutation at CpG codons of p53 gene
Author(s) -
Najjar Sadeghi Rouhallah,
Vahedi Mohsen,
Zojaji Homayon,
Zali Mohamad Reza
Publication year - 2013
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12053
Subject(s) - transversion , cpg site , methylation , dna methylation , gene , microbiology and biotechnology , biology , genetics , transition (genetics) , genome , mutation , gene expression
Objective Hypomethylation within the body of the p53 gene, which is normally methylated, has been found in neoplasms. Also, the CG → TA transition was not detected in the CpG codons of the p53 gene in gastritis lesions in Iranian patients. Therefore, an evaluation of the probable correlation between global genome methylation and alteration at CpG codons of p53 gene was needed. Methods For defining the genotypes of CpG codons, DNA sequencing was performed on 90 paired samples of gastritis and normal tissues. To measure global genome methylation status, the extracted DNA was digested with H pa II (methylation sensitive) and M sp I (insensitive). Then, enzymatic digestion was quantitated using Pyrosequencing as peak height. By calculating the H pa II/ M sp I peak ratio it is possible to evaluate the methylation level of normal and gastritis tissues.Results Codons 9, 245 and 248 underwent a CG → AT transversion but not a CG → TA transition. In addition, the mean methylation level was significantly different between the patients with GG and GT genotypes at codon 245 ( P = 0.019). Conclusions As CG → AT transversion at codon 245 is associated with global genome methylation, GG hypomethylation may induce different pattern of mutations, for example, C → A instead of C → T at the CpG codons of the p53 gene during gastritis development in Iranian patients.