The role of gene-gene and gene-environment interactions of polymorphic locuses of MMPs in the formation of hypertension in women
Objective. To study the role of gene-gene and gene-environment interactions of polymorphisms of matrix metalloproteinases with obesity and smoking in the formation of hypertension (HTN) in women. Design and methods. The study included genotyping data for seven polymorphic loci of MMPs - rs3025058, rs11568818, rs1320632, rs11225395, rs652438, rs243865 and rs17577 in 375 patients with HTN and 209 women in the controls. Genetic and environmental interactions involved in the HTN formation were detected using the Multifactor Dimensionality Reduction (MDR) method in Model-Based-MDR modification (MB-MDR vers. 2.6). The results were visualized in the MDR vers. 3.0.2 (http://sourceforge.net/projects/mdr). Results. Eight models of genegene interactions associated with the HTN formation in women (pperm ≤ 0,05) have been identified which are based on SNPs rs652438 MMP12, rs1320632 MMP8, rs3025058 MMP3 and rs11568818 MMP7. Eight models of interactions of locuses of MMPs with obesity and smoking (pperm < 0,002) were identified. Most of models include the polymorphic locus rs243865 MMP2. For the identified models, combinations of high (β = 0,76-2,06) and low (β = -0,37 - -1,23) risk of developing HTN were established. Conclusions. Our findings suggest that the polymorphic variants of MMPs and environmental factors have a synergistic effect in the formation of susceptibility to HTN.