Quantitative assessment of the influence of PSMA6 variant (rs1048990) on coronary artery disease risk

The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Recently, an association of a functional sequence variation, -8C/G, in the human proteasome subunit a type 6 gene (PSMA6) with the susceptibility to coronary artery disease (CAD) was reported. After that, several validation studies have been conducted among various ethnic populations, but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis of 15,991 cases and 16,784 controls from 10 case–control studies was performed. Potential sources of heterogeneity including ethnicity, sample size and HWE status of study were also assessed. In a combined analysis, the summary per-allele OR for CAD of the -8C/G polymorphism was 1.09 (95 % CI: 1.02–1.16; P = 0.006). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians for the polymorphism; while no significant associations were found among Caucasians and other ethnic population in all genetic models. When restricted to studies concerning myocardial infarction patients, significant associations were detected in all genetic models. Furthermore, significant difference of PSMA6 mRNA expression was found between genotypes. In conclusion, this meta-analysis suggests that G allele of PSMA6-8C/G polymorphism is a risk factor associated with increased CAD susceptibility, but these associations vary in different ethnic populations.