Effect of type 2 diabetes mellitus and mutations of the cyp2c19 gene on the platelets functional activity of patients with ischemic heart heart disease
Authors: Netiazhenko V , Karpenko O 
Published: October 2021

Abstract

Goal
To establish sensitivity to clopidogrel in carriers of various G681A alleles of the CYP2C19 gene on the basis of a comprehensive assessment of platelet hemostasis.

Materials and methods
We examined 120 patients with various forms of coronary heart disease (CHD), including: 60 patients with acute coronary syndrome (ACS), 60 patients with chronic coronary syndrome (CCS). All patients were treated with clopidogrel.

Results
Genotyping of patients revealed that 73.3% of the examined cohorts of patients with ACS and 86.4% of patients with CCS were dominated by the native genotype G/G. In the cohort of patients with ACS, the degree of spontaneous platelet aggregation (SPA) among patients with G/A-A/A genotype exceeded the control values by 4.6 times (p&lt;0.001). When compared with the corresponding indicator in patients with G/G genotype, it was found that the presence of a mutated A-allele had no significant effect on the increase in SPA (OR=2,450; 95% CI: 0.462–12.982; p=0.480). The degree and rate of arachidonic acid (AA)-induced platelet aggregation was significantly lower than the control values in all subgroups, but did not differ between subgroups of patients with different polymorphisms (OR=0.625; 95% CI: 0.065–6.090; p=0.912). Studying the degree and rate of ADP-induced platelet aggregation did not reveal statistically significant changes either in comparison with the control group or in the intergroup analysis. There was also no significant association between CYP2C19 gene polymorphisms and the degree of ADP aggregation (OR=0.795; 95% CI: 0.216–2.928; p=0.983).
In patients with stable CHD, despite the use of clopidogrel in all patients, the level of SPA was significantly higher than the control values and depended on the polymorphism of the CYP2C19 gene.
To evaluate the effect of diabetes on the effectiveness of inhibition of platelet functional activity by clopidogrel in carriers of different allelic variants of the CYP2C19 gene, we compared the G/G and G/A-A/A genotypes. The group of isolated coronary heart disease consisted of 48 patients with G/G genotype (80%) and 12 patients with mutated A-allele (20%). Patients with pathology of carbohydrate metabolism were distributed as follows: 47 patients had G/G genotype (78%), and 13 - G/A-A/A (22%). It was found that when carrying the G/A-A/A genotype, the intergroup difference was 72.6% (57.65 [49.34; 67.8] vs. 33.4 [32.47; 37.99], p&lt;0.01). The chance of encountering a high degree of ADP-induced aggregation among carriers of the A-allele of the CYP2C19 gene with diabetes was almost 17 times significantly higher than the group of patients with isolated coronary heart disease (OR=16,667 (2,273–122,218), p=0.009).

Conclusion
The data obtained in our study showed that the patients with CHD and concomitant diabetes mellitus who had a mutated A-allele CYP2C19 gene was less sensitive to clopidogrel, which was manifested in a higher degree of ADP-induced platelet aggregation.

Funding Acknowledgement
Type of funding sources: None.