INVESTIGATION OF ASSOCIATIONS BETWEEN PON1 -108C/T GENE POLYMORPHISM AND CLINICAL-NEUROLOGICAL, NEUROIMAGING, HEMODYNAMIC CHARACTERISTICS AND COGNITIVE DYSFUNCTION IN PATIENTS WITH VASCULAR ENCEPHALOPATHY IN CHRONIC CEREBRAL ISCHEMIA
DOI:
https://doi.org/10.11603/1811-2471.2023.v.i4.14299Keywords:
vascular encephalopathy in chronic cerebral ischemia, paraoxonase-1 (PON1), PON1 gene -108C/T polymorphism, clinical and syndromic characteristics, cognitive dysfunctionAbstract
SUMMARY. Oxidative stress is an essential part of the pathogenesis of vascular encephalopathy in chronic cerebral ischemia (CVE). Paraoxonase-1 (PON1) is the main blood enzyme that hydrolyzes oxidized lipids in lipoproteins, exhibiting significant antioxidant and cardioprotective effects depending on the polymorphism of the PON1 gene.
The aim – to study probable associations of the -108C/T polymorphic variant of the PON1 gene with clinical-neurological, neuroimaging, hemodynamic characteristics and cognitive dysfunction in patients with CVE.
Material and Methods. The study group included 145 patients with CVE, of which 18 patients underwent a molecular genetic study of the -108C/T polymorphic variant of the PON1 gene. The control group comprised 12 healthy individuals, who were selected to be representative in terms of both age and gender. Standard clinical-neurological, instrumental and neuropsychological research methods were used. A molecular genetic study of the -108C/T polymorphic variant of the PON1 gene was carried out in a molecular genetic laboratory of the State institution "Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine", Kyiv. Statistical processing of the results was carried out using “STATISTICA 13.0”.
Results. Analyzing the dependence of clinical neurological syndromes, neuroimaging, hemodynamic characteristics and cognitive dysfunction on the -108C/T polymorphic variant of the PON1 gene in patients with CVE, significant differences in the distribution of genotype frequencies were established only for clinical neurological syndromes (asthenic syndrome was detected in 100.00 % of carriers of the T/T genotype and in 66.67 % of carriers of the C/T genotype; c2=6.43; p=0.040) and cognitive dysfunction (75.00 % of patients with a moderate cognitive defect were carriers of the T/T genotype and 61.54 % of patients with a mild cognitive defect were carriers of the C/T genotype; c2=19.74; р<0.001).
Conclusions. The results indicate the advisability of further studying the association of the -108C/T polymorphic variant of the PON1 gene and cognitive functioning using a larger sample of patients with CVE, which will help explain the molecular mechanisms causing cognitive impairment and assess the diagnostic significance of including this polymorphism in the genetic panel of the investigation in patients with CVE.
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