Association Between Heme Oxygenase 1 Gene Promoter Polymorphisms and Susceptibility to Coronary Artery Disease: A HuGE Review and Meta-Analysis

We performed a systematic review and meta-analysis of heme oxygenase 1 gene (HO-1) promoter polymorphisms and susceptibility to coronary artery disease (CAD) based on eligible studies retrieved from electronic databases from 2002 to 2013. Eleven studies, involving 10,170 patients with CAD and 6,868 controls, were included. Overall, no significantly decreased risk of CAD was found in persons with the SS genotype of the HO-1 (GT)n repeat length polymorphism compared with those with the LL + SL genotype. However, decreased risks of CAD were observed in the Asian subgroup, the coronary-artery-narrowing ≥50% subgroup, the myocardial infarction subgroup, the age- and sex-matched subgroup, and the good-quality-reports subgroup. The primary heterogeneity in the studies came from age and sex matching and the extent of coronary stenosis. CAD risk was significantly decreased for persons with the AA genotype of the T(-413)A single-nucleotide polymorphism versus those with the TT genotype, but most of the studies showed that the allele distribution was inconsistent with Hardy-Weinberg equilibrium. In this meta-analysis, we found that the (GT)n SS genotype was associated with decreased risk of CAD after controlling for biases due to age and sex matching, extent of coronary stenosis, ethnicity, and study quality. The relationship between the T(-413)A single-nucleotide polymorphism and CAD should be interpreted more cautiously.