Abstract
BackgroundThe aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI.ResultsNeither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE ε4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women.In MCI patients such as synergistic effect was only found between AG and APOE ε4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01).ConclusionCOMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE ε4 allele that proves greater in women with AD.
Highlights
The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed
In the present study we analyzed a sample of 223 MCI patients, 345 AD patients, and 253 healthy control subjects without significant differences in terms of age (p > 0.05)
In MCI patients, this synergistic effect was only found between AG and APOE ε4
Summary
The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. The APOE gene explains only a fraction of the genetic risk associated with AD, and it is possible that other genes or metabolic factors may modify the APOE ε4 effect to initiate the pathogenesis of AD. One of these candidate genes is the COMT (Catechol-O methyltransferase) gene [2]. There is a single functional nucleotide polymorphism (SNP) on exon 4 of the COMT gene: rs4680 This SNP is characterised by low allele A activity (ATG/methionine) and a (high activity) allele G (GTG/valine) in codon 158. In contrast to the G (high activity) allele, the A (low activity) allele causes the accumulation of catecholestrogens [3]
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