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 (P<0.05) higher PGI levels than did the genotypes harboring a G allele (mean (s.d.)=66.9 (32.0) and 59.1 (30.7) microg ml(-1) 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.