Peculiaritie of Distribution of Polymorphic Variants of IL1Β Gene in Patients with Atherosclerosis and Metabolic Syndrome

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Author(s): Saranchina Yu.V*, Rossova NA, Khanarin NV, Kilina O. Yu, Dutova SV, Kulakova TS.

Journal Name: Current Pharmacogenomics and Personalized Medicine (Formerly Current Pharmacogenomics)

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Abstract:

Objective: The purpose of the study was to analyze the association of allelic polymorphism of IL1В gene C>T loci -31 and +3953 with atherosclerotic changes of arteries in patients with metabolic syndrome (MS).

Materials and Methods: The main group of the study included 30 consecutive patients (24 women and 6 men, mean age - 51.7±2.2 years), for examination and treatment in the therapeutic Department of the Republican clinical hospital named "G. YA. Remishevskaya" (Abakan) about arterial hypertension or suspicion of type 2 diabetes. The criteria for inclusion in the core group included: compliance with the MS criteria according to the IDF criteria (2006); and the presence of ultrasound markers of atherosclerosis (AS) according to the study of brachiocephalic arteries (presence of atherosclerotic plaques (ASP) and stenosis ≥30%). The control group included persons who underwent a planned medical examination in the Republican clinical hospital name "G. YA. Remishevskaya" (Abakan). A total of 35 patients (26 women and 9 men, mean age 44.7±1.5 years) were selected. The study involved the Russian population (Caucasians) living in the territory of the Republic of Khakassia.

All the necessary examination and data collection were conducted including anamnestic data, anthropometric examination (measurements of length and body mass, waist circumference) body mass index, laboratory examination of blood biochemical parameters (glucose and lipid) and instrumental examination (blood pressure measurement, conducting ECG and ultrasound the brachiocephalic arteries). Single-nucleotide polymorphisms (SNP) of the promoter region of the IL1B gene at position-31C/T (rs1143627) and polymorphism in the coding part of the gene in exon 5 +3953C/T (rs 1143634) were studied by restriction analysis of amplification products (RFLP analysis).

Results: The risk of development of AS in patients with MS may be higher in carriers of genotype TT (OR = 1,76; 95% CI: (0,96-3,24)) or T allele (OR = 1,44; 95% CI: (0,82-2,53)) IL1В gene in the polymorphic locus of the T-31С and genotype CT (OR = 1,85; 95% CI: (0,92-3,37)) or T allele (OR = 1,35; 95% CI: (0,63-2,89)) IL1В gene in the polymorphic locus of C + 3953T. The most common combination of gene polymorphisms IL1В was haplotype (-31) ТC/(+3953)СС in both the groups surveyed (40.6% to 36.8%, respectively). Variant (-31)TT/(+3953)CT in the main group was found significantly more often (15.8%, at χ2= 4.92, at p=0.03) than in the control group (3.1 %). The value of the odds ratio in this case was 3.99 (95% CI: (1.08-14.79), which indicates the risk of AS development against the background of MS in carriers of combined genotype inheritance (-31)TT/(+3953) CT.

Conclusion: The risk of development of AS in the background of MS is increased in carriers of combinations of SNPs (-31)TT/(+3953)CT IL1В gene responsible for hyper-production of this cytokine. In this connection, further studies of the association of genes with MS and AS components should focus on intergenic interactions.

Keywords: Gene polymorphism, atherosclerosis, metabolic syndrome, interleukin-1B, IL1В Gene, allelic polymorphism

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(E-pub Ahead of Print)
DOI: 10.2174/1875692117666190416150346