ACE and AT2R1 gene polymorphism in patients with chronic vascular encephalopathy: association with neuroimaging changes and cognitive functioning

Abstract

Background. Given the synergistic effect of the ACE and AT2R1 genes and their impact on the maintenance of homeostatic processes, the aim of our research was to identify the associations of the studied polymorphic variants of the ACE and AT2R1 genes with neuroimaging changes, data from arterial duplex ultrasound and cognitive functioning in patients with chronic vascular encephalopathy (CVE). Materials and methods. A retrospective analysis of 145 medical records of patients with CVE was conducted, of which 18 patients underwent a molecular genetic study. The control group consisted of 12 people representative in terms of age and gender. Neuroimaging was performed using multislice computed tomography or magnetic resonance imaging. The state of cerebral blood flow was studied using transcranial duplex ultrasound of intracranial and extracranial vessels. The cognitive functioning was tested using the Montreal Cognitive Assessment. Results. When analyzing the associations of polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene with neuroimaging changes and parameters of cerebral hemodynamics in CVE among carriers of I and D alleles of the ACE gene, a probable relationship was found between their frequency distribution and the presence/absence of gliosis phenomena (62.69 % of D allele carriers were diagnosed with gliosis, p < 0.05); a probable relationship between the frequency distribution of the D/D genotype of the ACE gene and the presence of angiospasm (in 72.73 % of patients), insufficiency of blood flow in the carotid system (72.73 % of cases) and vertebrobasilar insufficiency (in 36.36 % of people). When evaluating the dependence of cognitive functions based on the Montreal Cognitive Assessment score in patients with CVE on the polymorphic I/D variants of the ACE gene and A1166C of the AT2R1 gene, probable changes were revealed in the frequency distribution of genotypes and alleles of the polymorphic I/D variant of the ACE gene (χ2 = 11.33; p = 0.023), while all carriers of the D/D genotype have impaired cognitive functioning (moderate in 36.36 % and mild in 63.64 % of cases), which also corresponds to the frequency of the D allele distribution in this cohort of patients (29.63 % of people have a moderate cognitive impairment and 70.37 % — a mild cognitive impairment, p = 0.013). Conclusions. The study results indicate that the ACE gene may be involved in the development of neuroimaging changes and cognitive decline in CVE.