Profibrotic genetic polymorphisms as possible risk factors for the development of diastolic dysfunction in patients with epicardial adiposity

Abstract

Aim. To determine the associations of variable sites of fibrogenesis genes with the risk of left ventricular (LV) diastolic dysfunction (DD) in patients with epicardial adiposity (EA).Material and methods. The study included 101 men with general obesity (Altai Territory) without cardiovascular diseases, diabetes and documented LVDD, of which, after determining the epicardial fat thickness (EFT), 2 groups were formed: group 1 — with EA (EA+), EFT ≥7 mm or more (n=70); group 2 — without EA (EA-), EFT <7 mm (n=31). The control group was formed from Kemerovo region residents of the corresponding sex and age and without a history of cardiovascular diseases and general obesity. Polymorphisms of the MMP9 rs17576, TGFB1 rs1800469, MMP3 rs6796620, MMP3 rs626750, MMP1 rs514921, LOC101927143 rs4290029, TIMP2 rs2277698 genes were determined in all patients using the polymerase chain reaction. After 4,7±0,3 years, all patients with general obesity underwent repeated echocardiography to assess LVDD.Results. We found that in the group with EA for rs626750 MMP3, the carriage of the homozygous T allele is 2 times more common (recessive inheritance, p=0,0022). After 4,7±0,3 years, LVDD was registered in 18 patients in the EA+ group and in 2 patients in the EA- group. When analyzing inheritance patterns, as well as comparing genotypes in groups of patients with EA with developed LVDD (n=20) and without LVDD (n=78), we found that patients with EA and LVDD are 3,4 times more likely to be a carrier of the homozygous T allele (recessive inheritance, p=0,02) for rs1800469 TGFB1.Conclusion. In patients with EA and LVDD, the carriage of the T rs1800469 TGFB1 allele is more common, which probably contributes to cardiac fibrosis and LVDD according to a recessive inheritance.