Clinical significance of single nucleotide missense-mutation rs950880 of the IL1RL1 gene in patients with essential hypertension

Abstract

Modern cardiology requires the search for specific pathogenetically involved genemutations, the consequences of which can be considered in the management of patientswith hypertension. Scientists are targeting C/A polymorphism at the rs950880 position,which is associated with tissue expression of the IL1RL1 gene and the plasma level ofsoluble ST2 - a new biomarker in the diagnosis of cardiovascular disease. The aim ofthe study was to evaluate the association of rs950880 polymorphism of the IL1RL1 geneand the state of central and intracardiac hemodynamics in men with essentialhypertension (EН) of varying severity, residents of the Podillia region of Ukraine. 170men who met the inclusion criteria were examined according to a standard protocol,which included clinical, laboratory and instrumental examinations in accordance withcurrent recommendations. The subjects were divided into a control group of 70 menwithout cardiovascular disease and a study group of 50 men with asymptomatic EН and50 people with EH complicated by IIA stage chronic heart failure (CHF). Genotyping ofSNP rs950880 of the IL1RL1 gene was performed using an allele-specific polymerasechain reaction. All men in the control group and the study group underwent echocardiographywith Doppler according to the standard protocol. Statistical processing of the obtainedresults was performed in the package Statistica 12.0 using conjugation tables analysis,analysis of variance. It was found that among men living in Vinnytsia, Ukraine, carriers ofСС and CA SNP rs950880 of the IL1RL1 gene dominate (42.35 % and 45.30 % ofindividuals, respectively), AA homozygotes are significantly less common (12.53 %,p<0.05). Men without cardiovascular diseases and patients with EH do not differ significantlyin the frequency of different variants of the genotype of the studied gene. C\A polymorphismis not associated with the risk of EН. The homozygotes AA with EH have a significantlylower LV myocardial mass index (LVMMI) (69.14±6.90 g/m2.7, compared with homozygotesCC - 75.42±2.54 g/m2.7, and heterozygotes CA - 76.96±3.18 g/m2.7, p<0.05). Among thecarriers of the C allele, an "unfavorable" EН phenotype is mainly formed in the form of ahigh risk of LV hypertrophy (OR=11.36, 95 % СI=0.63-24.76, χ2=14.32, p=0.0008).Homozygotes AA in the rs950880 locus of the IL1RL1 gene, on the contrary, have a lowprobability of developing LV hypertrophy (OR=0.80, 95 % SI=0.02-0.42, χ2=14.32, p=0.0008)and its preserved systolic function. Thus, the SNP rs950880 of the IL1RL1 gene is notassociated with the risk of EH or its severity in residents of Vinnytsia, Ukraine. Carriageof the C allele is accompanied by the formation of an "unfavorable" EH phenotype with asignificantly high risk of LV hypertrophy.