Association between polymorphisms in glutathione S-transferase Mu3 and IgG titer levels in serum against Helicobacter pylori

Abstract

This study investigated the association between glutathione S-transferases (GST) polymorphisms and immunoglobin G (IgG) titer levels in serum against Helicobacter pylori (H. pylori). Out of a total 300 healthy subjects seropositive for H. pylori, we analyzed the relationship between 15 single-nucleotide polymorphisms (SNPs), namely two in GST-mu2 (GST-M2), five in GST-mu3 (GST-M3), four in GST-pi1 (GST-P1) and four in GST-theta2 (GST-T2), and IgG antibody titer levels in serum against cytotoxin-associated gene A (CagA) and the surface antigen of H. pylori (Hp), as well as the levels of pepsinogen I (PGI). Titer levels were classified by tertile. The age-sex adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the middle and low titer groups were calculated using a polytomous logistic regression model, with the high titer group considered as control. Results for GST-M3 showed a significant association between SNPs, CagA and Hp titers. In addition, the AA genotype (high enzyme activity) from SNP rs7483 (Val224Ile) in GST-M3 showed a significantly low risk for being in the low titer group (OR: 0.48, 95% CI: 0.27-0.86 and OR: 0.46, 95% CI: 0.26-0.83 for CagA and Hp, respectively). Furthermore, the AA genotype from the rs7483 SNP showed significantly (Po0.05) higher PGI levels than did the genotypes harboring a G allele (mean (s.d.)¼66.9 (32.0) and 59.1 (30.7) lg ml À1 for AA and AG+GG, respectively). Our results suggest that GST-M3 polymorphisms are associated with levels of IgG titer in serum against H. pylori. GST-M3 activity is possibly involved in protection against mucosal atrophy caused by H. pylori as the levels of IgG titer and PGI are linked to mucosal status.

Proteomic analysis of gastric cancer and immunoblot validation of potential biomarkers

“…They have been studied in relation to several cancers, GC included. For example, Martinez and colleagues have found no association with the GSTM3 genotype and GC risk [56] , whereas Tatemichi and co-workers have described a possible association between GSTM3 polymorphisms and Ig titer levels in serum against H. pylori [57] .…”

Genetic Factors Influence Serological Measures of Common Infections

“…Susceptibility to C. pneumoniae has been linked to genes encoding toll-like receptors, cytokines, and mannose-binding proteins [37,36] . Polymorphisms in a number of genes are associated with H. pylori infection, including those encoding cytokines, metalloproteinases, glutathionine transferase, cyclooxygenase-2, and other metabolically active molecules [38][39][40] . Infection with T. gondii has been associated with genes encoding interferon gamma, tolllike receptors, and the purinergic receptor P2X 7 [41][42][43] .…”

BMD Values and <b><i>GSTM3</i></b> Gene Polymorphisms in Combination with <b><i>GSTT1/GSTM1</i></b> Genes: A Genetic Association Study in Slovenian Elderly

“…The Ile allele of the Val224Ile polymorphism was suggested to decrease GSTM3 enzyme activity on the basis of determining serum IgG levels against Helicobacter pylori [22], although the enzyme activity itself was not determined. In our study, a borderline significant association of this SNP with BMD_fn and BMD_th, but not with BMD_ls, was observed.…”

“…The Ile allele of Val224Ile polymorphism was shown to decrease the enzyme activity, although this was determined indirectly [22]. GSTM3 gene also contains a 3-bp deletion in intron 6 (delAGG).…”