P3560Prospects for the use of integrated assessment of gene-candidates polymorphisms in the management of arterial hypertension: let's start

Abstract

Abstract Nowadays a large amount of data about the frequency of gene-candidates polymorphisms occurrence in patients with arterial hypertension (AH) have been accumulated. The using of single polymorphisms for diagnostic and prognostic purposes appeared to be not perspective. However multiple accumulation of gene-candidates polymorphisms in person is realized mostly in formation of AH. The purpose of the research was to compare the proportion of modified gene-candidates in a group of hypertensive patients with a similar group of non-hypertensive patients using the gene modification index (GMI) calculation for possible using in diagnostic and prevention of AH. Methods 180 patients with AH (age 54,2 [43–75], male/female 86/94) and 82 non-hypertensive patients (age 52,6 [42–71], male/female 38/44) were examined (ESC/ISH 2018). For comparative significance in the conducted research the patients under 40 years old were not included. Patients of both groups were perfomed the analysis of polymorphisms of the following candidate genes by PCR: ADD1:1378, AGT: 704, AGT: 521, AGTR1:1166, AGTR2: 1675, CYP11B2:-344, GNB3:825, NOS3:-786, NOS3:894. Then the GMI was formed where the proportion of “pathological” homozygous polymorphism of one gene was 1.5 points, the heterozygous polymorphism – 1 point, “normal” genotype – 0 points. Then points were summed up and formed the GMI as proportion of the “pathological” genotypes, expressed as a percentage. GMI is calculated by the formula: GMI = (N/13,5) × 100, where N is the sum of points of present genetic polymorphisms; N = n1 + n2 + n3 + n4 + n5 + n6 + n7 + n8 + n9; 13,5 – the maximum number of points of present genetic polymorphisms. The GMI from 0 to 20% was considered as low genetic risk, from 21 to 40% – moderate risk, from 41 to 70% – high risk, from 71 to 100% – very high risk. Results In hypertensive patients the low genetic risk was in 5% of cases, in the group of non-hypertensive patients - in 85.4% (p=0.0001); moderate genetic risk was observed in 22.2% of patients with AH and in 13.4% patients without AH (p=0.14); 52.2% of hypertensive patients and 1.2% of non-hypertensive patients had a high genetic risk (p=0.0001); a very high risk was in 20.6% of patients with AH and was absent in patients without AH (p=0.0001). The average mean of GMI in the group with AH was 64.2% [CI 95%, 30–78], in the group of non-hypertensive patients - 22% [CI 95%, 5–30], (p=0.0001). At the same time in GMI less than 25% there was no case of the presence of AH. Conclusions In the conducted research the representative data was obtained: the proportion of the modified gene-candidates significantly exceeded the proportion of the modified genes in non-hypertensive patients. It demonstratively shows the perspectivity of GMI using in the diagnostic and preventive management of patients with AH. GMI up to 25% mostly is not phenotypically realized and the probability of hypertension developing in these patients is extremely low.