The Role of the Stress Factor in Mediating the Genetic Predisposition to Stroke of the Background of Hypertensive Disease

Objectives. To study the interaction of polymorphic markers for matrix metalloproteinases (MMP) and chronic stress on formation of stroke on the background of hypertensive disease. Materials and methods. A total of 830 patients were studied: 303 patients with ischemic stroke on the background of hypertensive disease and 527 patients with hypertensive disease without stroke. SNP for metalloproteinases were studied using the real-time polymerase chain reaction. The functional significance and influences of polymorphic loci on gene expression were studied using the HaploReg (v4.1) (http://archive.broadinstitute.org) and GTEx-portal (http://gtexportal.org) services. Results and conclusions. An association was found between the GG rs11568818 genotype of the MMP7 gene and a high risk of developing stroke in patients experiencing regular stress (odds ratio (OR) 1.71). The 5A allele and the 5A/5A genotype of rs3025058 of the MMP3 gene had protective effects on development of stroke in people without histories of chronic stress (OR 0.73 and OR 0.60, respectively). The SNP studied here were located in the histone protein H3K4me1 and H3K4me3 region, which is hypersensitive to DNase 1 and binds regulatory proteins and transcription factors, while the polymorphic rs11568818 locus is linked with the level of expression of the MMP7 gene.