Abstract
Background. The study of the genetic phenotypes of CHF and the search for markers associated with the outcome of the disease may contribute to a better understanding of the pathophysiology of CHF and to target the therapeutic effects. Objective. To research the relationship between clinical, instrumental and genetic factors, including polymorphic variants of the genes HSPB7 (rs1739843), FRMD4B (rs6787362), rs10519210 of the locus 15q22 and MADD (rs10838692, rs2290149) with the survival of patients with postinfarction cardiosclerosis and CHF. Design and methods. The study included 506 men aged 55.4 ± 13.5 years with MI transferred more than 3 months ago. The main group consisted of 260 patients with HF-rEF (CHF I-IV FC, with LVEF (Simpson) <40%), reference group – 246 patients without CHF clinic with LVEF (Simpson)> 55%. The control group consisted of 257 healthy donors, comparable in sex and age. Prospective observation was performed by telephone contact. Results. Allele T and TT genotype polymorphic variant rs2290149 of the MADD gene were associated with the development of IHD and postinfaction cardiosclerosis (p1,2 <0,005). The highest occurrence of the T allele of both polymorphic variants rs2290149 and rs10838692 of the MADD gene was observed in patients with HFrEF (p1,2 <0,0001). CC genotype of polymorphisms (rs2290149, rs10838692) of the MADD gene is associated with a protective effect against IHD with postinfaction cardiosclerosis and, possibly, arterial hypertension, occurring in ≥68% of patients and acting as a competing pathological towards coronary artery disease. The CC genotype of the polymorphic variant rs1739843 of the HSPB7 gene was associated with a lower 3-year mortality in patients with IHD, regardless of LVEF and clinical manifestations of CHF (p <0.05). Conclusion. The findings confirm the need for further genetic analysis of a broader population of CHF patients with ischemic etiology.
Highlights
The study of the genetic phenotypes of CHF and the search for markers associated with the outcome of the disease may contribute to a better understanding of the pathophysiology of CHF and to target the therapeutic effects
The main group consisted of 260 patients with HF-rEF (CHF I-IV FC, with LVEF (Simpson) 55%
Allele T and TT genotype polymorphic variant rs2290149 of the MADD gene were associated with the development of IHD and postinfaction cardiosclerosis (p1,2
Summary
У пациентов с СН-нФВ, по сравнению с референтной группой, более часто встречалась ФП, сахарный диабет (в 99% случаев СД 2 типа) , отягощенная наследственность по ССЗ: в 31,2% и 14,4%, 24,9% и 14,4%, 34,2% и 22,8%, соответственно (все р < 0,05). Респонденты без клинических проявлений ХСН имели чаще артериальную гипертензию (АГ) в анамнезе и ожирение, в 83,3% и 31,7% по сравнению с основной группой, где эти состояния диагностировались в 68,5% и 28,1% случаев, соответственно (р1,2 < 0,01). На момент включения в исследование группы не различались по давности возникновения АГ, которая в среднем составила 11 лет, однако давность ИБС была существенно выше в основной группе, составив 10 лет против 6,8 лет в референтной группе (р< 0,0001). Распределение генотипов и аллелей полиморфных вариантов rs2290149 и rs10838692 гена MADD в исследуемых группах
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