Study of associations between the -108C/T Polymorphism of the PON1 gene and clinical syndromes, neuroimaging changes indicated by transcranial doppler sonography of cerebral vessels, and cognitive dysfunction in patients with chronic alcohol-induced encep

Abstract

Objective — to establish probable associations of the -108C/T polymorphic variant of the PON1 gene with clinical-neurological, neuroimaging hemodynamic characteristics, and cognitive dysfunction in patients with Chronic Alcohol-Induced Encephalopathy (CAIE). Materials and methods. A total of 102 patients with CAIE undergoing inpatient treatment at Ternopil Regional Clinical Psychoneurological Hospital during 2021—2022 were examined, and 26 patients underwent molecular genetic research. The control group consisted of 12 healthy individuals, matched for age and gender. Clinical and neurological examinations followed a standard protocol, neuroimaging of the brain was conducted using multispiral computed tomography or magnetic resonance imaging, cerebral blood flow was studied using transcranial duplex scanning on a Philips HDI device (the Netherlands); and cognitive functions were assessed using the Montreal Cognitive Test (MoCA). Molecular genetic research of the -108C/T polymorphic variant of the PON1 gene was performed in the molecular genetic laboratory of the State Institution «Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine», Kyiv. Statistical data analysis was conducted using the «Statistica 13.0» software. Results. Analysis of the dependence of clinical-neurological syndromes, neuroimaging, hemodynamic characteristics, and cognitive dysfunction based on the results of the MoCA test on the -108C/T polymorphic variant of the PON1 gene in patients with CAIE revealed significant differences in genotype distribution only concerning cognitive dysfunction (χ2 = 10.13, p = 0.038). Notably, carriers of the T/T genotype predominated among individuals with a moderate cognitive defect (66.67 %), while carriers of the S/T genotype were more common among those with a mild cognitive defect (62.50 %). Regarding the distribution of allele frequencies of the -108C/T polymorphic variant of the PON1 gene in patients with CAIE, it was determined that among individuals with a moderate cognitive defect, 83.33%, and among those with a mild cognitive defect, 62.50 % were carriers of T alleles (χ2 = 6.93, p = 0.031). Conclusions. The study results suggest the need for further exploration of the association between the allelic polymorphism of the PON1 gene and cognitive functioning involving a larger sample of CAIE patients. This will help elucidate the molecular mechanisms underlying cognitive disorders and assess the diagnostic significance of including the -108C/T polymorphic variant of the PON1 gene in the genetic panel for early diagnosis of cognitive disorders and dementia prevention.