Associations of the single nucleotide polymorphism rs2228145 of the IL6R gene with features of the clinical course of hypertrophic cardiomyopathy

Introduction. The study of modifiable cardiometabolic risk factors (CMRFs) influencing the clinical phenotype of hypertrophic cardiomyopathy (HCM) is currently relevant. It is known that modifier genes can affect the course and progression of symptoms in HCM. At the same time, the analysis of associations between single nucleotide variants of the interleukin-6 receptor gene (IL6R) and the specifics of the clinical course of HCM remains a poorly studied area.

The objective was to investigate the associations of the SNP rs2228145 of the IL6R gene with HCM, the presence of arterial hypertension (AH) in patients with HCM, age at diagnosis and serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6).

Methods and materials. The analysis of the SNP rs2228145 of the IL6R gene was conducted in 218 adult patients with HCM aged >18 years (median 53 [35.3; 64] years) and in 200 individuals from a comparison group (general population).

Results. It was found that the CC genotype was more common in the group of patients with HCM than in the general population (p=0.005). Carriage of the CC genotype of rs2228145 was associated with a 3.64-fold increased risk of HCM (OR=3.64; 95 % CI: 1.44–9.15; p=0.005). The CC genotype of rs2228145 of the IL6R gene was more prevalent among HCM patients with concomitant AH (n=134) compared to HCM patients without AH (14.9 % vs. 2.4 %, p=0.003) and was associated with a 7.29-fold increased risk of AH in HCM patients (OR=7.29; 95 % CI: 1.62–32.85; p=0.003) relative to the AA genotype. The C allele predominated in the HCM+AH group compared to the HCM without AH group (35.4 % vs. 25.6 %, p=0.03) and was associated with a 1.6-fold increased risk of AH in HCM patients (OR=1.6; 95 % CI: 1.04–2.45; p=0.03). Among HCM patients with concomitant AH aged ≥45 years (n=119), the age at diagnosis in CC genotype carriers was lower than in carriers of the AA and AC genotypes (59 [54.5; 62] years vs. 63 [57.3; 69.8] years, p=0.03). Serum CRP and IL-6 concentrations were higher in HCM patients aged ≥45 years with overweight or obesity than in HCM patients of the same age group with normal body weight: CRP – 2.9 [1.28; 4.23] mg/L vs. 1.4 [0.3; 2.42] mg/L (p=0.04); IL-6 – 1.42 [0.89; 3.37] pg/mL vs. 0.19 [0.11; 0.74] pg/mL (p=0.004), respectively.

Conclusion. Carriage of the CC genotype of the rs2228145 variant of the IL6R gene increases the risk of HCM by 3.64-fold. Carriage of the CC genotype of rs2228145 is associated with a 7.29-fold increased risk of AH in HCM patients, while carriage of the C allele is associated with a 1.6-fold increased risk of AH in these patients. In HCM patients with concomitant AH aged over 45 years, carriage of the CC genotype was associated with a 4-year earlier diagnosis compared to carriers of the AA and AC genotypes. In HCM patients aged ≥45 years with overweight or obesity, serum CRP and IL-6 concentrations are higher than in normal-weight individuals of the same age.

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