Аллельный полиморфизм генов, вовлеченных в продукцию IL-1β, и предрасположенность людей к развитию артериальной гипертензии

Abstract

Background: The level of IL-1β in blood plasma is determined not only by pro-inflammatory stimuli, but also by allelic polymorphism of the IL1B and NLRP3 genes. Information on the associa-tion of allelic polymorphism of these genes with the risk of arterial hypertension (AH) is scarce and contradictory. The aim of the study: To assess the risk of developing hypertension in carriers of various allelic variants according to the polymorphic markers rs1143634 (c.3953C>T), rs16944 (c.-511T>C), rs1143627 (c.-31C>T) of the IL1B gene and rs35829419 (c.2113C>A) of the NLRP3 gene, as well as to study possible mechanisms for the inclusion of allelic polymorphism of these genes in the etiology and pathogenesis of AH. Materials and methods: 182 DNA samples from healthy people and 180 DNA samples from patients with hypertension (stages I-II) were used for genotyping rs1143634, rs16944, rs1143627 (PCR-RFLP analysis). 215 DNA samples from healthy individuals and 180 hypertensive patients were used to determine alleles and genotypes for rs35829419 of the NLRP3 gene (allele-specific PCR with TaqMan probes). Total RNA obtained from peripheral blood leukocytes (PBL) of 45 healthy people and 50 patients with AH (27 people taking metoprolol or bisoprolol for more than a year and 23 people without antihypertensive thera-py) for assessment of gene expression by real-time PCR was used. The content of pro-inflammatory proteins in the blood plasma of 40 healthy individuals was measured by ELISA. Results: Carriers of the TT genotype for the c.3953C>T marker of the IL1B gene were found to have a 3-fold increased risk of AH (OR=3,239; 95% CI: 1,858-5,649). In healthy individuals with this genotype, the con-tent of IL-1β in blood plasma and the expression of the ICAM1 gene in PBL are higher than in het-erozygotes or homozygotes for the C allele (p=0,029 and p=0,004, respectively). Individuals with the TT genotype for the c.-31C>T marker of the IL1B gene had a reduced risk of АН (OR=0,645; 95% CI: 0,481-0,866). IL1B gene expression and hsCRP levels were lower in healthy individuals with the T allele for rs1143627 (p=0,022, p=0,040, respectively). There were no differences in the distribution of allele and genotype frequencies for markers c.-511T>C of the IL1B gene and c.2113C>A of the NLRP3 gene in the studied groups. Conclusion: Polymorphic markers rs1143634 (c.3953C>T) and rs1143627 (c.-31C>T) of the IL1B gene are probably involved in the predisposi-tion of the inhabitants of Karelia to the development of arterial hypertension.