Polymorphism of CYP3A4 isoenzyme gene in patients with chronic rheumatic heart disease

AIM: This study aimed to identify the associations of CYP3A4 isoenzyme gene polymorphism with the parameters of echocardiography (EchoCG), spirometry, and endothelial function of patients with chronic rheumatic heart disease (CRHD).

MATERIALS AND METHODS: A total of 128 patients with CRHD (15.6% men and 84.4% women) were examined. A392A, A392G, and G392G polymorphic markers were genotyped through polymerase chain reaction (PCR) with an SNP-EXPRESS electrophoretic scheme (NPF Litekh, Russia) to detect results after DNA was isolated from leukocytes in venous blood. EchoCG was implemented on an Affinity 50 apparatus (Philips, the Netherlands), endothelial function was assessed with an AngioScan01 apparatus (AngioScan-Electronics, Russia), and respiratory function was examined using a SpiroLab II spirometer (MIR Medical, Italy).

RESULTS: The distance in a 6 min walk test did not show any significant differences among the groups: A392A − 327.47 ± 6.71 m, A392G − 303.63 ± 26.19 m, G392G − 338.87 ± 20.12 m (p=0.505). The area of the mitral opening was as follows: A392A − 1.74 (1.67; 1.81) cm2, A392G − 1.68 (1.45; 1.92) cm2, and G392G − 1.65 (1.67; 1.81) cm2 (p = 0.214). As for the EchoCG parameters, the group of G392G homozygotes had the lowest linear dimensions of the left ventricle (the end diastolic dimension − 4.83 (4.72; 4.95) cm, the end systolic dimension − 2.97 (2.79; 3.14) cm, the right ventricle (2.45 [2.32; 2.58] cm), of the right atrium (4.09 [3.56; 4.62] cm), and the criteria of left ventricular hypertrophy (thickness of the interventricular septum 0.88 [0.81; 0.95] cm, and the posterior wall − 0.88 (0.81; 0.95 cm). No statistically significant differences were found in the occlusion index amplitude among the groups, that is, single nucleotide replacements of CYP3A4 had no influence on the system of low-resistance arteries. Conversely, the values of the phase shift between channels (reflecting the condition of large arteries) significantly differed. The G392G polymorphism showed the worst parameters, and minimal changes were observed in the A392A group. Contour analysis demonstrated the highest augmentation index values in the G392G group, reflecting the maximal stiffness of vessels. The CYP3A4 polymorphism had no effect on the parameters of respiratory function in the studied cohort of patients. Spirometry revealed that the obstructive and restrictive parameters were not significant although homozygotes demonstrated the highest forced vital capacity of the lungs (76.5% [71.1% and 82.0%]) and forced expiratory volume for 1 s (84.6% [79.0% and 90.3%]). The maximal parameter of the vital capacity of the lungs in homozygotes for A392A (85.6% [82.3% and 88.8%]).

CONCLUSION: Patients with CRHD homozygous for G392G had the minimum parameters of hypertrophy and dimensions of the left ventricular cavity. They also had the lowest values for the cavities of the right heart. CYP3A4 polymorphism had no effect on the parameters of respiratory function in the studied patients with CRHD.