Gender-specific protective effect of the −463G>A polymorphism of myeloperoxidase gene against the risk of essential hypertension in Russians

•Polymorphism −463G>A of the MPO gene is negatively associated with hypertension.•The variant MPO genotypes had a protective effect against hypertension in females.•Mechanisms by which MPO gene is involved in hypertension pathogenesis are proposed.

The purpose of this study was to investigate whether a common polymorphism −463G>A (rs2333227) in the promoter of myeloperoxidase (MPO) gene, an oxidant enzyme producing hypohalogenic radicals, is associated with the risk of essential hypertension (EH) in Russian population. A total of 2044 unrelated subjects including 1256 EH patients and 788 normotensive controls were recruited for this study. Genotyping of the MPO gene polymorphism was done using TaqMan-based assay. A genotype −463GA was associated with decreased risk of EH (odds ratio = 0.82; 95% confidence interval: 0.68-1.00) at a borderline significance level (P = .05). The gender-stratified analysis showed that a carriage of the −463GA and −463AA genotypes is associated with decreased EH risk only in females (odds ratio = 0.74, 95% confidence interval: 0.56-0.96; P = .02). To the best of our knowledge, this is the first study reporting a negative association between the −463G>A polymorphism of the MPO gene and EH risk. Molecular mechanisms by which MPO gene is involved in the pathogenesis of EH are discussed.