engleski

The association between the catechol-o-methyltransferase (COMT) genotypes with cognition in dementia

Introduction: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by different phases of cognitive decline. In AD, there is a progressive impairment of acquired cognitive abilities while subjects with MCI show less severe cognitive disturbances. Cognitive dysfunction develops as a result of the complex interactions between multiple genetic, epigenetic, developmental, and environmental factors. Among many genes involved in cognition is the gene coding for catechol- O-methyltransferase (COMT), the enzyme responsible for the degradation of dopamine, resulting in the modulation of dopaminergic function. Therefore, COMT genetic variants were studied in various dementias characterized by cognitive loss. The aim of the study was to evaluate the possible association between COMT rs6269 and COMT rs4680 polymorphisms and cognitive decline in subjects with AD and MCI. Methods: Cognitive deterioration was assessed with the Mini-Mental State Examination (MMSE) and the Clock Drawing test (CDT) scores in 193 patients with AD and 269 subjects with MCI. COMT rs6269 and COMT rs4680 (Val158Met) were genotyped using the real-time PCR. Multiple linear regressions and Kruskal Wallis ANOVA were used to detect the association of the COMT rs6269 or COMT rs4680 genotypes with cognitive decline. Results: Multiple linear regression showed that COMT rs6269 was significantly associated with MMSE and CDT scores and these effects were affected by diagnosis and COMT rs6269 genotypes and age. In contrast, multiple linear regression revealed that COMT rs4680 was not significantly associated with MMSE or CDT scores, and the only significant effects were found for age and diagnosis. To further evaluate the effect of COMT polymorphisms on cognition, all subjects were subdivided into AA, GA, or GG genotype carriers of the COMT rs6269 or COMT rs4680, respectively, and according to MMSE or CDT scores. Carriers of the GG genotype of the COMT rs6269 had significantly (p=0.007) lower CDT scores than AA carriers, while other genotype groups did not differ significantly according to the CDT or MMSE scores. Conclusion: Although COMT rs4680 (Val158Met) was reported to be related to cognitive loss in various neuropsychiatric disorders, present results revealed a significant association between the other COMT polymorphism, rs6269, with cognitive deterioration in dementia.

Alzheimer's disease ; catechol-o-methyl-transferase ; cognition ; dementia ; genetic variants

nije evidentirano