PB0511 - Model of P2RY12 -T-744C, (GPIbα) - C482T, NOS3 - T-786C, MTHFR - C667T Gene Interactions in Patients with High Cardiovascular Risk

Background: Multifactorial vascular damage is reflected by the presence of a significant number of biochemical markers, including a variability of platelet reactivity. The association of the haplotype of H2 presence with peripheral arterial damage due to gene interactions is undetermined.

Aims: to present the model of P2RY12 -T-744C, (GPIbα) - C482T, NOS3 - T-786C, MTHFR - C667T gene interactions in patients with high cardiovascular risk.

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 isolation DNA from leukocytes and polymerase chain reaction (PCR). For statistical analysis of the obtained results we used softwares MDR 3.0.2 (USA) and GMDR 0.7 (USA).

Results: To evaluate epistatic or complementary interaction of the genes we modeled the interaction of nucleotide polymorphisms by the method of multifactorial dimensional reduction (MDR). According to the analysis of this method in the sample of sick and healthy people, the optimal models of combinations of gene interactions were determined, with the establishment of their accuracy and reproducibility. As a result, we selected 2 models with the highest degree of reproducibility (10/10 - 100%) - for three loci of polymorphism and for four loci of polymorphism, table I.
The MDR method, when constructing a model of interaction, additionally defines classification rules (if-then rules) for combinations of genotypes for assigning carriers of established combinations to the main or control group, which will allow to predict the probability of vascular complication, table II.

Conclusion(s): The risk of macrovascular complications in patients with hypertension and diabetes mellitus type 2 associated with allelic polymorphism depends not only on the type of monolocus polymorphism, but has a more complex nature of dependence due to intergenic multidirectional interactions.