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Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas.

ABSTRACT: AIM:To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma. METHODS:Primary gastric carcinomas (n=80), their corresponding normal mucosal samples, and gastric mucosal biopsies from normal/gastritis control patients (n=54) were used. Hypermethylation at -253 nt and -251 nt in relation with the translational start site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter were analyzed by Bst UI-combined bisulfite assay (COBRA), denaturing high performance liquid chromatogram (DHPLC), and sequencing. RESULTS:(A) The specific methylation at -253 nt and -251 nt was observed in 2 of 60 primary gastric carcinomas, but neither in all of the corresponding mucosa nor in normal/gastritis samples, by Bst UI-COBRA and DHPLC. (B) The hMLH1 promoter was methylated homogeneously in the xenograft of the primary gastric carcinoma with the methylated and unmethylated hMLH1. (C) The pattern of SNP at -93 nt of the hMLH1 promoter in 54 Chinese patients with gastric carcinoma was the same as that in the control patients: 51 % was A/G heteroalleles, 34 % and 15 % were A/A and G/G homoalleles, respectively. CONCLUSION:Biallelic inactivation of hMLH1 by epigenetic silencing existed in human primary gastric carcinoma homogeneously. Hypermethylation of hMLH1 may play a role in the early stage of development of a few gastric carcinomas. The SNP at -93 nt is not related to the susceptibility of gastric carcinomas.

SUBMITTER: Deng DJ

PROVIDER: S-EPMC4728242 | biostudies-literature | 2003 Jan

REPOSITORIES: biostudies-literature

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Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas.

Deng Da-Jun DJ Zhou Jin J Zhu Bu-Dong BD Ji Jia-Fu JF Harper Jeffrey C JC Powell Steven M SM

World journal of gastroenterology 20030101 1

<h4>Aim</h4>To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma.<h4>Methods</h4>Primary gastric carcinomas (n=80), their corresponding normal mucosal samples, and gastric mucosal biopsies from normal/gastritis control patients (n=54) were used. Hypermethylation at -253 nt and -251 nt in relation with the translational start site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter were ...[more]

PMID: 12508345

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Project description:BackgroundThe aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of MTHFR rs1801133 single nucleotide polymorphism (SNP) and MTHFR promoter methylation with hypertension among Taiwanese adults.MethodsWe retrieved data including, MTHFR promoter methylation, MTHFR rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB).ResultsThe distributions of hypertension and MTHFR promoter methylation quartiles (β < 0.1338, 0.1338 ≤ β < 0.1385, 0.1385 ≤ β < 0.1423, and β ≥ 0.1423 corresponding to <Q1, Q1-Q2, Q2-Q3, and ≥Q3) among individuals with the rs1801133 genotypes (CC, CT, and TT) were significantly different (P < 0.05). The risk of hypertension was significantly higher among individuals with the TT genotype compared to the reference genotype (CC): odds ratio (OR); 95% confidence interval (CI) = 2.718; 1.503-4.914. The trend of the association of the CT and TT genotypes with hypertension was dose-dependent (P-trend = 0.0041). MTHFR promoter methylation (lower quartiles compared to ≥Q3) was not significantly associated with hypertension. However, its interaction with MTHFR rs1801133 was significant (P = 0.0323). After stratification by rs1801133 genotypes, lower MTHFR promoter methylation quartiles (<Q1, Q1-Q2, Q2-Q3) compared to ≥Q3 were significantly associated with a higher risk of hypertension among individuals carrying the CC genotype: ORs (95% CIs) = 3.225 (1.140-9.124), 4.177 (1.424-12.247), and 8.645 (2.513-29.739) for Q2-Q3, Q1-Q2, and <Q1, respectively. The trend test was significant (P-trend = 0.0009).ConclusionIndependently, rs1801133 TT was associated with a higher risk of hypertension, but methylation was not. Based on genotypes, lower methylation was dose-dependently associated with a higher risk of hypertension in individuals with the CC genotype. Our findings suggest that MTHFR rs1801133 and MTHFR promoter methylation could jointly influence hypertension susceptibility.

Dataset Information

Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas.

Publications

Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas.

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