Background/Purpose: Rheumatoid arthritis (RA) and hypertension (HT) are multifactorial polygenic diseases. The incidence of hypertension in patients with RA is higher than in the general population, ranging from 20 to 60%. The role of genetic polymorphisms in the development of this comorbidity is investigated, but there is little information on the subject. So, potentially promising is the study of the prognostic value of gene promoter polymorphism of endothelial nitric oxide synthase NOS3 T-786C (rs2070744) in patients with RA. Additionally NOS3 plays an important role in the regulation of vascular tone, angiogenesis, osteogenesis, inflammation. The aim of the study was to investigate the prevalence of NOS3 T-786C (rs2070744) gene promoter polymorphism in patients with RA and RA associated with hypertension.

Methods: The study involved 148 patients with RA (100% women) aged 47.0 [42.8; 52.0] years, disease duration 78 [48; 120] months, moderate and high disease activity (DAS28> 3.2). The diagnosis of RA was established by ACR/EULAR (2010) criteria. Polymorphism of NOS3 Т786С gene (rs2070744) was performed by PCR (Real-Time PCR, Bio-Rad iCycler IQ5) using a set of «SNP-express» (NPF “Lyteh”, Russia). All studied polymorphism satisfied Hardy-Weinberg equilibrium (χ2 test, p> 0.05). The study was conducted in accordance with the Declaration of Helsinki of the World Medical Association “Ethical principles of medical research involving human subjects” (2000), the requirements of GCP, the applicable national legislation. Statistical analysis of the results was performed by methods of variation statistics in the application package SPSS22 (© SPSS Inc.).

Results: Among the patients with RA normotensive were 83 (56.1%) and 65 (43.9%) patients were hypertensive. In 44 (29.7%) patients with RA hypertension was registered after the onset of RA. In patients without hypertension (n = 83), the frequency of genotypes was as follows: T/T – 43.3% (36 pts) T/C – 44.6% (37 pts), C/C – 12% (10 pts). In RA patients with hypertension (n = 65), the frequency of genotype C/C was significantly higher – 30.8% (20 pts); χ2 = 8,44, p <0.01), and the frequency of genotype TT was conversely lower – 29.8%, than in RA patients without hypertension. Analysis of the common and recessive inheritance patterns showed that patients with RA, carriers of CC genotype, have 3 times higher risk of developing hypertension (OR = 3,24; 95% CI 1,39-7,55) compared to T/T and T/C genotype carriers. Analysis of the dominant inheritance model showed that patients with RA, presence of T/T genotype was characterized by tendency (χ2 = 3.12; p = 0.08) to decrease the risk of hypertension compared to T/C and C/C genotype (OR = 0.54, 95% CI 0.27-1.07).

Conclusion: The association of T786C NOS3 (rs2070744) gene promoter polymorphism with the development of hypertension in patients with rheumatoid arthritis in the Ukrainian population was established. In RA patients the presence of genotype C/C increased risk of hypertension.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/endothelial-nitric-oxide-synthase-gene-polymorphism-as-a-risk-factor-of-hypertension-in-patients-with-rheumatoid-arthritis/