The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers
| Autor: | Jessica Castro Flores, Sandra Inglés Borda, Manuel Fernández Martínez, M.C. González-Fernández, María Carrasco Zabaleta, Miryam Barandiarán Amillano, María Ángeles Gómez Beldarraín, Josefa Moraza López, Marian M. de Pancorbo, Xabier Elcoroaristizabal Martín, Begoña Indakoetxea Juanbeltz, Rocio Bereincua Gandarias, Ana Molano Salazar, Nuria Ortiz Marqués, Luis Galdos Alcelay, Juan María Uterga Valiente |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Apolipoprotein E haplotypes genotype Apolipoprotein E4 Neuropsychological Tests decline Risk Factors Genotype Odds Ratio estrogen replacement therapy psychosis Prospective Studies genes Aged 80 and over Genetics Reverse Transcriptase Polymerase Chain Reaction General Neuroscience lcsh:QP351-495 CELLULAR AND MOLECULAR NEUROSCIENCE allele Middle Aged Diagnostic and Statistical Manual of Mental Disorders Regression Analysis Female Restriction fragment length polymorphism Alzheimer's disease Psychology Research Article medicine.medical_specialty Catechol O-Methyltransferase Polymorphism Single Nucleotide lcsh:RC321-571 Cellular and Molecular Neuroscience Sex Factors Alzheimer Disease Internal medicine medicine Humans Genetic Predisposition to Disease conversion Allele lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry epsilon-4 Alleles Aged Analysis of Variance Catechol-O-methyl transferase organic chemicals Patient Selection Haplotype Odds ratio medicine.disease lcsh:Neurophysiology and neuropsychology Cross-Sectional Studies Endocrinology age bacteria Cognition Disorders |
| Zdroj: | BMC Neuroscience Addi. Archivo Digital para la Docencia y la Investigación instname BMC Neuroscience, Vol 10, Iss 1, p 125 (2009) |
| ISSN: | 1471-2202 |
| Popis: | 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. Supported in part by grants from Federacion de Asociaciones de Familiares de Enfermos de Azheimer de Euskadi, Fondo de Investigacion Sanitaria del Instituto Carlos III ( Madrid), Pfizer Foundation and Ayudas a la Investigacion de la Obra Social de la Caja Vital Kutxa. |
| Databáze: | OpenAIRE |
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