Background: Phenotypic manifestations of platelet aggregation may be modified by allelic polymorphism of genes associated with platelet functions and increases the risk of vascular complications. In the studies have shown that the occurrence of H2-haplotype is associated with increased platelet ADP dependent aggregation with different concentrations of inducers, which may be due to increased platelet ADP receptor expression.

Aims: to establish gene-gene interactions allelic between polymorphisms P2RY12–744C, (GPIbα)-C482T, NOS3 – T-786C, MTHFR – C667T, P2RY12 -T-744C, (GPIbα) – C482T in patients with hypertension and diabetes mellitus type 2.

Methods: The study included 100 patients with hypertension and diabetes mellitus type 2 (main group) with defined macroangiopathies and 50 healthy people (control group). The distribution of allelic polymorphisms was investigated by PCR. For statistical analysis of the obtained results we used DeFinetti online programs (https://ihg.gsf.de/cgi-bin/hw/hwa1.pl).

Results: According to this model, in the main and control group for the GPIbα gene the frequency of “risk” alleles was 53% and 38%, for the P2RY12 gene – 36% and 28%, for the NOS3 gene – 51% and 34%, for the MTHFR gene – 46% and 33%, with a total median frequency of 48,5% for the main group and 33,5% for the control group. On average, there were 1,33 alleles per person in the control group, and 1.86 alleles in the main group, which was in 1,42 folds greater (t = 3.07; p = 0,022; p = 0,04 by median Mood test). Thus, in contrast to the single-locus model of allelic polymorphism, carriers of “risky” allelic polymorphisms simultaneously for all 4 genes significantly (p < 0,05) increases the likelihood of macrovascular complications (table).

Conclusion(s): The risk of macrovascular complications in patients with hypertension and diabetes mellitus 2 is a measure of the effect of a combination of polymorphisms of the four so-called “risky” alleles.

Table

GRS for two-locus, three-locus, and four-locus models of vascular complications in patients with hypertension and diabetes type 2

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-p2y12-receptor-polymorphism-and-gene-gene-interactions-in-patients-with-high-cardiovascular-risk/