参与IL-1β产生的基因的等位基因多态性和人们患动脉高血压的易感性

L. Topchieva, I. Kurbatova, I. E. Malysheva, V. Korneva, Anna V. Topchieva
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引用次数: 1

摘要

背景:血浆中IL-1β的水平不仅与促炎刺激有关,还与il - 1b和NLRP3基因的等位基因多态性有关。关于这些基因的等位基因多态性与动脉性高血压(AH)风险之间的关系的信息是稀缺和矛盾的。本研究目的:根据IL1B基因多态性标记rs1143634 (C . 3953c >T)、rs16944 (C .- 511t >C)、rs1143627 (C .- 31c >T)和NLRP3基因rs35829419 (C . 2113c >A)评估不同等位基因变异携带者发生高血压的风险,并研究这些基因的等位基因多态性参与AH病因和发病机制的可能机制。材料与方法:采用182份健康人DNA样本和180份高血压患者(I-II期)DNA样本进行rs1143634、rs16944、rs1143627基因分型(PCR-RFLP分析)。采用TaqMan探针检测NLRP3基因rs35829419的等位基因和基因型,检测了215份健康个体和180例高血压患者的DNA样本。从45名健康人及50名AH患者(27名服用美托洛尔或比索洛尔一年以上,23名未接受降压治疗)的外周血白细胞(PBL)中获取总RNA,用实时荧光定量PCR方法评估基因表达。采用ELISA法测定40例健康人血浆中促炎蛋白的含量。结果:il - 1b基因c.3953C>T标记TT基因型携带者患AH的风险增加3倍(OR= 3239;95% ci: 1858 - 5649)。该基因型健康人血浆中IL-1β的含量和PBL中ICAM1基因的表达均高于C等位基因的纯合子和纯合子(p= 0.029和p= 0.004)。具有il - 1b基因c - 31c >T标记物TT基因型的个体患АН的风险降低(OR= 0.645;95% ci: 0,481-0,866)。携带rs1143627 T等位基因的健康个体IL1B基因表达和hsCRP水平较低(p=0,022, p=0,040)。IL1B基因C - 511t >C和NLRP3基因C - 2113c >A标记的等位基因分布和基因型频率在两组间无差异。结论:IL1B基因多态性标记rs1143634 (c.3953C>T)和rs1143627 (c. 31c >T)可能参与了卡累利阿居民动脉高血压的易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Allelic polymorphism of genes involved in IL-1β production and predisposition of people to the development of arterial hypertension
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.
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