Falls in elderly patients and their association with genetic factors

Objective. To evaluate the possibility of preventing falls in elderly patients with comorbid cardiovascular pathology by optimizing pharmacotherapy based on pharmacogenetic parameters. Materials and methods. We studied 172 medical records of people over 65 years of age with comorbid cardiovascular pathologies undergoing treatment in a multidisciplinary hospital in Moscow for the period from 2017 to 2020. All of them underwent blood sampling for genotyping by polymorphisms CYP2D6*4, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A5*3, CYP3A4*22 by polymerase chain reaction — PCR (real-time PCR). All the data obtained were analyzed in pairs using conjugacy tables. To determine statistical reliability, Pearson's -2 methods and Fisher's exact criterion were used. The genotype distribution was checked for compliance with the Hardy–Weinberg equation. To confirm the calculations obtained, mathematical models were additionally constructed using logistic regressions with step-by-step filter selection. The values of p < 0.05 were considered reliable. Results. The genotyping data was analyzed in comparison groups: 40 patients who had a fall in the last year, and 132 patients without falls. According to the results of the pharmacogenetic study, there was no significant (statistically) difference between patients from our sample with and without falls in the history of CYP2D6*4, CYP2C19*2, CYP2C19*3, CYP2C19*17, CYP3A5*3, CYP3A4*22 polymorphisms and CYP2C19 gene phenotypes. However, a wider range of data was obtained when assessing genotypes in subgroups of patients according to the therapy taken and the presence of concomitant pathology. The predominance of heterozygous and minor genotypes (CT/TT) according to CYP2C19*17 was noted in collapsed patients taking beta-blockers in ophthalmic and oral forms simultaneously (p = 0.05). A predominance of the heterozygous genotype, characterized as an "intermediate" metabolizer, was found among the fallen patients in the subgroups taking enteric acetylsalicylic acid according to the CYP2C19*2 (GA/AA) polymorphism (p = 0.044), in those taking inhaled glucocorticoids of the CYP2C19*17 (CT) polymorphism (p = 0.047) and phenotypic variants of the gene CYP2C19 (p = 0.029), in patients taking alpha-blockers of the CYP3A5*3 (GA) polymorphism (p = 0.026). Patients with falls and diabetes mellitus (as a concomitant disease) have a history of heterozygous genotype (GA) for CYP3A5*3 (p = 0.006), which correlates (p = 0.01) with data from a subgroup of patients taking hypoglycemic therapy. Conclusion. Thus, closer attention to patients with heterozygous and minor genotype variants in order to prevent falls is highly justified. It is necessary to consider the possibility of analyzing the likelihood of falls, to ensure that drugs are prescribed in lower doses, if possible, and to monitor the state of health of elderly patients more closely.