Patent RU-2762958-C1 (RU)
Title: Method for predicting the risk of developing coronary heart disease based on genetic testing data
Inventor: MESHKOV ALEKSEJ NIKOLAEVICH
IPC: A61B5/145
Filed: 2021-08-30
Granted: 2021-12-24
Abstract: FIELD: medicine. 
     SUBSTANCE: invention relates to medicine, namely to cardiology. The article describes a method for predicting the risk of developing ischemic heart disease (IHD) in individuals based on the data of genetic diagnostics using the next generation sequencing (NGS) method. The fact of the presence of rare and low-frequency NSVs is revealed. Then, on the basis of rare and low-frequency NSVs selected according to the criteria in the genes LDLR, AROV, PCSK9, AROS2, AROA5, LPL, ANGPTL3, AROSZ and ANGPTL4, they are divided into two groups: NSV with an increased risk of IHD and NSV with a reduced risk of IHD, and each NSV receives a score corresponding to the risk, while the group of rare and low-frequency NSV with an increased risk of IHD includes: all selected rare and low-frequency NSV of the LDLR gene, with the exception of NSV rs72658867, and the sign is assessed 4 points for each minor allele of NSV of the LDLR gene; all selected rare and low-frequency NSVs of the LPL gene, APOC2 and APOA5, and the trait is evaluated at 2 points for each minor allele of the NSV of the LPL, APOC2 and APOA5 genes; rare and low-frequency NSVs of the AROB and PCSK9 genes associated with the development of familial hypercholesterolemia, and the trait is estimated at 2 points for each minor allele of the selected NSV of the AROM and PCSK9 genes. The group of rare and low-frequency NSVs with a reduced risk of CHD includes: all selected rare and low-frequency NSVs of the ANGPTL3 and ANGPTL4 genes, and the trait is estimated at (-1) point for each minor NSV allele of the ANGPTL3 and ANGPTL4 genes; rare and low-frequency NSVs of the AROV, PCSK9 and AROSZ genes, leading to the development of familial hypobetalipoproteinemia, and the trait is estimated at (-1) point for each minor allele of the selected NSV; rare and low-frequency NSVs rs11591147 of the PCSK9 gene and rs72658867 of the LDLR gene, and the trait is estimated at (-0.5) points for each minor allele of the selected NSVs. To take into account the combined effect of several rare and low-frequency NSV genes LDLR, AROV, PCSK9, AROS2, AROA5, LPL, ANGPTL3, AROSZ, ANGPTL4 in a patient, the scores obtained for each allele, each rare and low-frequency NSV are summed up. Based on the obtained total score for rare and low-frequency NSVs, patients are divided into 3 main groups: with a score for rare and low-frequency NSVs of 2 points or more - with a very high genetic risk of developing coronary artery disease; with a point value for rare and low-frequency NSV (-0.5) points or less - with a reference genetic risk of developing coronary artery disease; with a score value for rare and low-frequency NSVs from 0 to 1.5, for which, additionally, based on the genetic analysis of genotypes of 59 frequent NSVs, the value of a single scale of genetic risk for 59 frequent NSVs (ShGR59) is calculated using the formula. In this case, the minimum value of ShGR59 was (-4.416) points, the maximum value of ShGR59 (-2.01) points, and the value for the 50th percentile was ShGR59 (-3.186) points. After determining the ShGR59for frequent NSVs, all patients with a score for rare and low-frequency NSVs from 0 to 1.5 are additionally divided into 2 groups: with a high genetic risk of developing coronary artery disease, and with a value of SHGR59 more than (-3.186) points ((-3.186 ) - the value for the 50th percentile ShGR59, experimentally obtained in the group of participants in this study); with a minimally increased genetic risk of developing coronary artery disease, and with a value of ShGR59 (-3.186) points or less. Based on the results obtained, it is concluded that there is a very high risk of developing IHD in individuals from the group with a very high genetic risk of developing IHD, a high risk of developing IHD in individuals from the group with a high genetic risk of developing IHD, and a relatively low risk of developing IHD in individuals from groups with minimally increased genetic risk of developing IHD and with a reference genetic risk of IHD. With a very high or high risk of developing IHD, the patient is referred to a therapist or cardiologist for diagnostics of IHD, registration and early initiation of preventive and therapeutic measures. With a relatively low risk of developing IHD in a patient, the absolute risk of developing IHD is not zero, and therefore such patients are recommended to assess cardiovascular risk based on current clinical guidelines. The invention makes it possible to identify persons with an increased risk of developing IHD. 
     EFFECT: increasing the efficiency of predicting the risk of developing IHD, especially in young people. 
     1 cl, 1 dwg, 5 tbl