Genetic polymorphisms in glutathione S-transferases T1, M1 and P1 and susceptibility to reflux esophagitis

Abstract

Recent studies indicate that the prevalence of reflux esophagitis (RE) in China is increasing. RE is one of the most common esophageal complications associated with gastroesophageal reflux disease (GERD) and RE-Barrett's esophagus-esophageal adenocarcinoma (EAC) sequence has been considered as an histogenesis model for EAC in Western countries. RE is only present in a subset of patients with GERD, suggesting an altered susceptibility to RE may exist in these GERD individuals. However, the genetic changes related with high susceptibility to RE is largely unknown. The polymorphisms in glutathione S-transferases (GSTs) T1, M1 and P1 have been reported with high susceptibity to esophageal cancer in Chinese people. The present case-control study was thus undertaken to characterize the genetic polymorphisms of GSTs and their correlation with susceptibility to RE. One hundred and nine patients with RE, 97 patients with nonerosive reflux disease (NERD) and 97 normal controls were recruited in this study. All the subjects were from Beijing, China, and received endoscopic examination and questionnaires for RE. Genomic DNA was extracted from the lymphocytes of peripheral blood for each subject. Genotypes of the GSTM1 and GSTT1 genes were analyzed by a multiplex PCR method. A-->G polymorphism of codon 104 of the GSTP1 gene was detected using PCR-based restriction fragment length polymorphisms (RFLP). The variant GSTP1 genotypes (*A/*Bomicron*B/*B) was found with a high frequency in the case with RE (40%), and followed by NERD (25%) and normal control (22%). The differences were statistically significant (P < 0.05). The risk for RE increased 2.42-fold [odds ratio (OR); 95% confidence interval (95% CI), 2.42 (1.22-4.80)] in the subjects with variant GSTP1 genotype. The subjects with positive variant GSTP1 genotypes and negative H. pylori infection showed increasing tendency for risk of RE [OR (95% CI), 2.67 (1.06-6.70)]. However, the subjects with GSTT1 and GSTM1 polymorphisms did not show any correlation with high risk for RE or NERD. No significant interactions were identified between the variant GSTs and cigarette smoking, or alcohol drinking and subtype of RE. The present result suggests that GSTP1 genetic polymorphism may be one of the high susceptibility factors involved in the mechanisms of RE. H. pylori infection may play a protective role against RE.

Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

“…Our results, however, are in disagreement with those of a previous study that suggested association between GSTP1 variants (alone or in interaction with H. pylori infection) and susceptibility to reflux esophagitis in the China population (Liu et al 2006). In our study, patients with GSTP1*B allele had no significantly increased risk for development of reflux esophagitis alone.…”

“…Although several studies have been undertaken to examine the association between susceptibility to some type of cancer (Morita et al 1998;Tan et al 2000;Lee et al 2000;De Bruin et al 2000) and genetic polymorphism in GSTs, there are limited data on their association with reflux esophagitis (Liu et al 2006). The aim of this study was to analyze associations of the GST polymorphisms with reflux esophagitis and BE, and their interactions with smoking status and H. pylori infection in influencing the susceptibility to develop these complications of GERD in the Czech population.…”

Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: Evidence from an updated meta-analysis

“…Therefore, the study by Yu et al [26] was the major source of the heterogeneity in this gene-gene interaction analysis and might have some differences compared to other studies in the selection of controls, or other undefined aspects. For instance, control subjects were selected from HBsAg carriers in the Yu et al study [26] while control subjects in other studies were mainly from healthy controls [18,24,34,35,38,39], and this discordance in the selection of controls among different publications might possibly lead to between-study heterogeneity. Furthermore, meta-regression analysis also suggested that the source of controls might be a major source of heterogeneity in GSTM1-GSTT1 interaction analysis, which further validated the hypothesis above.…”

“…These 24 individual case-control studies were published from 1997 to 2009 with 14 in English [19,22,23,[25][26][27]29,30,32,[35][36][37][38]40] and 9 in Chinese [18,20,21,24,28,31,33,34,39]. Table 1 presents a brief description of these 24 case-control studies.…”

Genetic factors in the pathogenesis of gastroesophageal reflux disease

“…Individuals homozygous for the null allele lack GST enzyme activity and hence may not be able to detoxify the chemicals [29,30]. However, GSTT1 and GSTM1 polymorphisms may not be associated with risk of GERD, though GSTP1 b allele was associated with susceptibility to GERD [31], especially to BE [32].…”