Associative role of polymorphism of the gene of MMP-9 (rs11697325) in development of arterial hypertension in patients with the rheumatoid arthritis

Aim. To study a contribution of polymorphism A-8202G (rs11697325) of a gene of matrix metalloproteinase-9 (MMP-9) in development of arterial hypertension (AH) in patients with the rheumatoid arthritis (RA).

Materail and methods. 143 patients with RA were examined, among which a group of patients with RA without AH (n=50) and a group of patients with RA in association with AH (n=93) were identified. Healthy volunteers (n=151) were also divided into 2 groups comparable in age, sex and number with the main groups (control group 1 – n=54, control group 2 – n=97). The work used a range of clinical, laboratory, instrumental methods. A molecular genetic study was also performed. Blood samples were taken from all study participants. DNA isolation was carried out by the standard phenol-chloroform method. Genotyping for the MMP-9 gene was performed by PCR-RFLP analysis (polymerase chain reaction – restriction fragment length polymorphism). PCR was carried out with a set of primers to the corresponding regions of the genome. PCR products were analyzed by electrophoresis in 4% polyacrylamide gel followed by staining with ethidium bromide.

Results. In the course of a molecular genetic study, a statistically significant predominance of the homozygous AA genotype and the A allele of the MMP-9 (rs11697325) gene polymorphism was observed in the group of patients with RA, both separately and in association with AH, in comparison with the data of control groups. The risk of developing RA estimated by the odds ratio (OR) in carriers of the AA genotype of the MMP-9 gene is 1.8 times higher (95% confidence interval – CI – 1.136–2.950; p=0.02) than in carriers of the GG and GA genotypes; in carriers of the A allele, the risk of developing RA is 1.6 times higher compared to the G allele (95% CI 1.119–2.578; p=0.01). The OR risk of developing RA in association with hypertension in carriers of the AA genotype of the MMP-9 gene is 2.8 times higher (95% CI 1.283–6.54; p=0.04) compared to GA and GG genotypes, 2.1 times higher in carriers of the A allele (95% CI 1.113–4.127; p=0.02) compared to the G allele.

Conclusion. Thus, the results of the study indicate that the homozygous AA genotype and the A allele of the MMP-9 (rs11697325) gene polymorphism are the predictors of the development of RA both as a separate nosological unit and in association with AH.