engleski

Catechol-o-methyl-transferase val158/met polymorphism in Alzheimer’ s Disease

Alzheimer disease (AD) is a neurodegenerative disease characterised by progressive cognitive decline, functional impairment, and psychotic symptoms. An enzyme catechol-O- methyltransferase (COMT) degrades dopamine and noradrenalin, and might be a risk factor for different psychiatric disorders, cognitive deficits and psychosis. COMT val158/met polymorphism results in guanine to adenine substitution at the exon 4 of the COMT gene (i.e. valine to methionine substitution). The presence of valine allele (high activity) is associated with up regulation of striatal dopamine activity and increased risk for psychosis in AD. Aim: The study evaluated the frequency of the COMT genotypes: GG (Val/Val), GA (Val/Met), and AA (Met/Met) in patients with psychotic and non-psychotic AD and in healthy controls. Methods: Probable AD fulfilling NINCDS-ADRDA criteria was diagnosed in 198 patients (DSM-IV-TR criteria): 63 with late and 135 with early onset (AD started after/before 65 years of age). Cognitive impairment was assessed using Mini Mental Status Examination (MMSE). In DNA samples COMT polymorphism was genotyped by TaqMan (Applied Biosystems) analysis. Results: The sample did not differ significantly (p>0.50) from Hardy-Weinberg equilibrium. Significant ( 2 =12.763 ; df=2 ; P = 0.002) differences in the frequency of the GG, GA or AA genotypes between 284 healthy control subjects (12%, 70% and 18%) and patients with AD (23%, 57% and 20%) ; or between healthy subjects and psychotic and non-psychotic patients with AD ( 2 =13.769 ; df=2 ; P = 0.008), or between healthy subjects and patients with early or late onset of AD ( 2 =13.315 ; df=2 ; P = 0.010) were found. MMSE scores did not differ significantly (F=2.103 ; df=2, 74 ; P = 0.129) between patients who had GG (16.58  6.4), GA (11.81  8.8), and AA (12.24  8.6) genotype. The distribution of the COMT genotypes did not differ significantly between 68 psychotic and 130 non-psychotic patients ( 2 =0.962 ; df=2 ; P = 0.618), or between patients with early or late onset of AD ( 2 =0.459 ; df=2 ; P = 0.795) were detected. Conclusion: Present results do not support the association of valine allele with psychosis, or methionine allele with better cognitive function in patients with AD. COMT polymorphism should be evaluated in larger groups with better cognitive characterisation.

Alzheimer disease; COMT val158/met polymorphism; Mini Mental Status Examination; early ad late onset; psychotic symptoms

Indexed / Abstracted in: Neuroscience Citation Index ; EMBASE / Excerpta Medica