engleski

Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia and mild cognitive impairment

A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment (MCI), various dementias and cognitive disruptions in schizophrenia. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex ; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neurocognitive tests. Peripheral blood samples were collected from 40 dementia and 13 MCI patients. The determination of the neurological status of the dementia patients utilized the MMSE, NPI, ADAS-COG, CDT, World pairs learning and recall/ Picture pairs learning and recall test and Visual attention test performed by an experienced neurologist. DNA from blood was extracted using the DNeasy Blood and Tissue Kit (Qiagen). In DNA samples COMT polymorphism was genotyped by a TaqMan (Applied Biosystems) analysis. The results, expressed as means &plusmn ; ; SD, were evaluated using one-way ANOVA followed by the Tukey’ s test. The Hardy-Weinberg analysis was used to test the equilibrium of the population. The differences in the genotype and allele frequencies were evaluated using a  2 test. Patients with dementia and MCI differed significantly (p=0.035-0.001, ANOVA) in age, duration of disease, MMSE, modified MMSE, ADAS, NPI, NPI apathy and CDT scores. The observed genotype distribution in patients with dementia ( 2=0.14 ; d.f.=1 ; P=0.933) and MCI ( 2=0.00 ; d.f.=1 ; P=1.000) did not differ significantly from the expected Hardy– Weinberg equilibrium. In patients with dementia, but not with MCI, significant (p=0.016-0.041, ANOVA) genotype-induced differences were found in scores for MMSE, modified MMSE, VAT duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly (p=0.015-0.037, Tukey's test) lower scores of MMSE or modified MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neurocognitive tests in carriers of Met/Met genotype in patients with dementia, but not in patients with MCI, compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neurocognitive test results than Met/Val or Val/Val genotype, our data on demented patients did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.

catechol-o-methyltransferase (COMT Val158/108Met) polymorphism; cognitive function; dementia; mild cognitive impairment

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