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Background  Oxidative stress is considered to be involved in the pathogenesis of coronary heart disease (CHD). Glutathione-S-transferase (GST) enzymes play important roles in antioxidant defenses and may influence CHD risk. The present meta-analysis was performed to investigate the link between glutathione S-transferase M1 ( GSTM1 ) null genotype and CHD and to get a precise evaluation of interaction between  GSTM1  null genotype and smoking by the case-only design.   Methods  PubMed and EMBASE databases were searched through 15 December 2020 to retrieve articles. Odds ratios (ORs) were pooled using either fixed-effects or random-effects models.   Results  Thirty-seven studies showed that  GSTM1  null genotype was associated with risk of CHD in total population, Caucasians and Asians (for total population, OR = 1.38, 95% confidence interval (CI): 1.15, 1.65; for Caucasians, OR = 1.34, 95% CI: 1.04, 1.72; for Asians, OR = 1.40, 95% CI: 1.11, 1.77). After adjustment for heterogeneity, these relationships were still significant. After adjustment for heterogeneity, case-only analysis of 11 studies showed a positive multiplicative interaction between  GSTM1  null genotype and smoking (ever smoking vs. never smoking) (OR = 1.27, 95% CI: 1.08, 1.50;  I 2   = 0%,  P =0.553).   Conclusions  The overall results indicated that  GSTM1  null genotype was associated with a higher risk of CHD, and the association may be affected by smoking status. This is the first meta-analysis to prove a positive effect of the interaction between  GSTM1  null genotype and smoking status on the risk of CHD. Well-designed studies are needed to investigate the possible gene–gene or gene–environment interactions.

An updated meta-analysis showed smoking modify the association of GSTM1 null genotype on the risk of coronary heart disease