The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers
Fernández Martínez, Manuel
Elcoroaristizabal Martín, Xabier
Galdos Alcelay, Luis
Castro Flores, Jessica
Uterga Valiente, Juan MarÍa
Indakoetxea Juanbeltz, Begoña
Gómez Beldarrain, María Angeles
Moraza López, Josefa
González Fernández, María Carmen
Molano Salazar, Ana
Bereincua Gandarias, Rocío
Inglés Borda, Sandra
Ortiz Marqués, Nuria
Barandiaran Amillano, Miryam
Carrasco Zabaleta, María
Martínez de Pancorbo Gómez, María de los Angeles
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BMC Neuroscience 10 : (2009) // Article n. 125
Background: 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. 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. Results: Neither 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 epsilon 4 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 epsilon 4 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). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.
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