Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia [Asocijacijska studija funkcionalnog polimorfizma katehol-o-metiltransferaze i kognitivnih funkcija u bolesnika s demencijom]

Nedić, Gordana and Borovečki, Fran and Klepac, Nataša and Mubrin, Zdenko and Hajnšek, Sanja and Nikolac, Matea and Muck-Šeler, Dorotea and Pivac, Nela (2011) Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia [Asocijacijska studija funkcionalnog polimorfizma katehol-o-metiltransferaze i kognitivnih funkcija u bolesnika s demencijom]. Collegium Antropologicum, 35 (S. 1). pp. 79-84. ISSN 0350-6134

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Abstract

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 and in various dementias. 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 neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (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 lower scores of 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 neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia 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 neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.

Abstract in Croatian

Funkcionalni polimorfizam Val158/108Met katehol-o-metiltransferaze (COMT), koji se odlikuje zamjenom valina (Val) i metionina (Met), povezan je s kognitivnim funkcijama u normalnom mozgu, starijom dobi i raznim demencijama. Katehol-o-metiltransferaza je odgovorna za razgradnju dopamina i drugih kateholamina, posebice u frontalnom korteksu. Stoga je za očekivati da nosioci alela s nižom aktivnošću enzima (Met) imaju bolje rezultate određenih neurokognitivnih testova. Studija je obuhvatila 46 bolesnika s demencijom i 46 zdravih starijih ispitanika. Bolesnicima je utvrđeno neurološko stanje koristeći test MMSE (od eng. Mini Mental Status Examination) i niz različitih neuroloških testova. Na uzorcima DNA provedena je genotipizacija. Bolesnici s demencijom su pokazali značajne, o genotipu ovisne, razlike u provedenim testovima. U odnosu na nosioce Val/Val genotipa, nosioci genotipa Met/Met su imali značajno niže rezultate na MMSE, značajno duže vrijeme trajanje, vrijeme odgovora i prosjek odgovora brojeva na testu vizualnog povezivanja (eng. Visual Association Test; VAT) te znatno veći veći broj neodgovorenih pitanja na testu WPLCR/PPLR (od eng. Word Pairs Learning and Recall/Picture Pairs Learning and Recall). Preliminarni rezultati su pokazali da bolesnici s demencijom, koji su nosioci genotipa Met/Met, ostvaruju značajno lošije rezultate na različitim neurokognitivnim testovima u odnosu na bolesnike nosioce genotipova Val/Val ili Val/Met. Iako bi genotip Met/Met trebao biti povezan s više raspoloživog dopamina u frontalnom korteksu, što se povezuje s boljim rezultatima neurokognitivnih testova u tih bolesnika, naši podaci nisu potvrdili tu hipotezu. Kako bi se razjasnila uloga polimorfizma COMT u kognitivnim funkcijama, potrebne su daljnje studije s većim brojem ispitanika.

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