Features of the distribution of polymorphic variants of candidate genes and clinical presentation of long-term period in patients with myocardial infarction and diabetic nephropathy
Authors: Siverina A , Skorodumova E A , Kostenko V , Pivovarova L , Ariskina O , Fedorov A , Skorodumova E G 
Published: October 2021

Abstract

Objective
To evaluate rate of distribution of the NOS3, APOE, SLCO1B1 and CYP2C19 genes and features of clinical presentation of the long-term period (12 months) in patients with myocardial infarction (MI) and diabetic nephropathy (DN).

Materials and methods
Examined 160 patients treated for MI (Males – 58,2%; 41,8% – females, average age 67,1±4,2 years). Patients were divided into 2 groups: the first (I) – 84 patients with MI and DN, the second (II) – 76 persons with MI without DN. The samples were comparable by sex and age. Determination of genotypic accessories genes NOS3 (rs2070744), APOE (rs769452), CYP2C19 (rs4986893 and rs4244285) and SLCO1B1 (rs4149056) were based on the analysis of genomic human DNA by polymerase chain reaction. The long-term follow-up period was 1 year.

Results
Analysis of the distribution of alleles of the gene NOS3 (T786C), affecting the synthesis of nitric oxide showed that polymorphic allele C 2 times more often detected in the group with MI and DN– 38,7%, compared to the comparison group 17,1%, p&lt;0,05. T- allele was statistically more frequent in II-82,9% than in I-61,3%, p&lt;0,05. Polymorphism (Leu28Pro) of the APOE gene, potentiating hyperlipoproteinemia, the Pro allele was more often detected in group I – 8,9%, than in group II – 1,3%, p&lt;0,05. Analysis of allele expression features of the SLCO1B1 gene polymorphism (Val174Ala), which affects the metabolism of statins, did not revealed a significant difference between the groups, p&gt;0,05. Polymorphic variants (G681A and Trp212Ter) of CYP2C19 gene, determining sensitivity to clopidogrel, had the following characteristics: allele *1 was more frequently detected in the control group – 96,7%, relative to the Ist – 88,7%, p&lt;0,05. Allele *2 was leader in patients with MI and DN – 8,9%, compared to control 2,0%, p&lt;0.05. Distribution of allele *3 between groups did not differ statistically in I – 2,4%, II – 1,3%, p&gt;0,05. Clinical presentation of the long-term period (12 months): hospitalizations of patients due to decompensated chronic heart failure (CHF) in I – 19,1%, in II – 6,6%, p&lt;0,05. Recurrences of acute coronary syndrome (ACS) met 3 times more often in group I – 15,5%, versus 5,3% in the second group, p&lt;0,05. Stent thrombosis: 6 times more frequent in the group with MI and DN, compared to the control group of 1,3%, p&lt;0,05. Long-term mortality: I – 15,5%, II – 4,0%, p&lt;0,05.

Conclusions
In patients with MI and DN, polymorphic alleles of the NOS3, APOE, and CYP2C19 genes are statistically more common, which probably has an additional aggravating effect on the course of disease in the long-term period (1 year).
In the group of patients with MI and DN, for a long-term period (1 year), it is statistically more often complicated by CHF decompensation, recurrent ACS, and stent thrombosis, which finally led to fatal outcomes with mortality rate 14,7%.

Funding Acknowledgement
Type of funding sources: None. Distribution of genetic variantsPresentation of the long-term period