HYPERTROPHIC CARDIOMYOPATHY IN THE OLDER AGE GROUP: THE EFFECT OF CARDIOMETABOLIC RISK FACTORS AND RS2290149 AND RS10838692 OF THE MADD GENE

Abstract

Objective. To study the impact of cardiometabolic risk factors and polymorphic variants rs2290149 and rs10838692 of the MADD gene on myocardial remodeling in the elderly patients with hypertrophic cardiomyopathy (HCM). Design and methods . We enrolled 257 patients with left ventricular hypertrophy (LVH) of various origin (mean age 57,7 ± 11,2 years; men — 5 %, women — 48 %): HCM (n = 154) and LVH caused by cardiometabolic risk factors (n = 103). The control group included 288 healthy donors. A standard clinical (laboratory and instrumental) diagnostic methods were applied. Genotyping for SNPs rs2290149 and rs10838692 of the MADD gene was performed using real time polymerase chain reaction (PCR). Results . Pre-obesity and obesity in patients with HCM were associated with increased left ventricular (LV) posterior wall thickness (14,82 ± 3,6 versus 12,77 ± 3,69 mm, respectively, p = 0,01), but not with the LV mass index and the interventricular septum. Obese HCM patients had greater detection rate of the symmetrical LVH (64 versus 10 % in non-obese HCM patients, p = 0,001). We observed a significant increase in frequency of TT genotype of rs2290149 and rs10838692 of the MADD gene in patients with LVH of various origin compared to healthy group: 81,6 vs. 71,5 % (ТТ : ТС+СС, p = 0,007) and 54,1 vs. 43,1 % (ТТ : ТС+СС, р = 0,002), respectively. The allele frequency also differs for rs2290149 (T : C = 89,6 : 10,4 % vs. 82,3 : 17,7 %; odds ratio (OR) = 1,864, 95 % confidence interval (CI) 1,306 to 2,660; p = 0,01) and for rs10838692 (T : C = 72,6: 27,4 % vs. 62,2 : 37,8 %; OR = 1,611, 95 % CI 1,246 to 2,082; p = 0,01). We found a significant increase in frequency of TT genotype of rs10838692 of MADD gene in patients with HCM 55,2 % (ТТ : ТС+СС, р = 0,019) and LVH caused by cardiometabolic risk factors — 52,4 % (ТТ : ТС+СС, p = 0,014) compared to healthy group (43,1 %). We also detected a trend towards the predominance of the TT genotype in rs2290149 of the MADD gene in patients with LVH caused by cardiometabolic risk factors (80,4 %) (ТТ : ТС+СС, р = 0,097), reaching a statistical significance in the HCM group (82,5 %) (ТТ : ТС+СС, р = 0,025) compared to healthy group (71,5 %). The allele frequency also differs for rs2290149 (T : C = 89,9 : 10,1 %, p = 0,01 in HCM; 89,2:10,8 %, р = 0,04 in LVH caused by cardiometabolic risk factors) versus 82,3 : 17,7 % in control group and for rs10838692 (T : C = 72,4 : 27,6 %, p = 0,01; 72,8 : 27,2 %, р = 0,01, respectively) versus 62,2 : 37,8 % in control. Conclusions . Pre-obesity and obesity in patients with HCM led to a greater LV posterior wall thickness and symmetrical myocardial remodelling. The T allele and TT genotype of SNPs rs10838692 and rs2290149 of the MADD gene were associated with the presence of LVH of various origin in the older subjects, but do not affect the degree of myocardial hypertrophy. Patients with HCM showed greater frequency of simultaneous carriage of the TT genotype and сombined carriage of the T allele of the polymorphic variants rs10838692 and rs2290149 of the MADD gene compared to the control group. The presence of obesity/overweight in patients with combined carriage of the TT genotype and simultaneous carriage of the T allele is associated with a greater thickness of the LV posterior wall, an increase in the left atrium size and the LV end-diastolic dimension.