The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers
- Equal contributors
1 Neurology Department, Hospital de Cruces, Baracaldo, Vizcaya, Spain
2 Research General Service, Bank of DNA and Dpt. of Z. and Cellular Biology, Faculty of Pharmacy, University of Basque Country UPV/EHU, Vitoria-Gasteiz, Álava, Spain
3 Neurology Department, Hospital de Txagorritxu, Vitoria-Gasteiz, Álava, Spain
4 Neurology Deparment, Hospital de Basurto, Bilbao, Vizcaya, Spain
5 Neurology Department, Hospital Donosti, San Sebastian, Guipuzcoa, Spain
6 Neurology Department, Hospital de Galdakao, Galdakao, Vizcaya, Spain
7 Neurology Department, Hospital Santiago Apóstol, Vitoria-Gazteiz, Álava, Spain
BMC Neuroscience 2009, 10:125 doi:10.1186/1471-2202-10-125Published: 30 September 2009
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.
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 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).
COMT (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.