Catechol-O-Methyltransferase Gene Polymorphism and Its Potential Role in the Development and Progression of Mild Cognitive Impairment

Mild cognitive impairment (MCI) is defined as a decline in memory, concentration, and logical and abstract thinking that represents an intermediate stage between normal cognitive function and dementia. Patients with MCI are characterized by a significantly higher risk of both dementia development and premature mortality compared to physiologically healthy subjects. Genome-wide association studies (GWAS) have revealed many polymorphisms associated with the risk of developing MCI, which makes them a promising tool for the early diagnosis and pharmacological correction of MCI. Polymorphic variants of the catechol-O-methyltransferase (COMT) gene, one of the key enzymes involved in dopamine catabolism, appear to be among the most promising for inclusion in the diagnostic panel of MCI. Analysis of COMT gene variants opens up opportunities for the patient risk stratification and the development of personalized pharmacogenetic approaches to therapy. In this brief review we consider clinically significant polymorphic variants of the COMT gene, their impact on the physiological functions of the enzyme, as well as current possibilities and the feasibility of pharmacological correction