The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers.
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 epsilon4 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 respectively). In AD patients this effect was greater in women.In MCI patients such as synergistic effect was only found between AG and APOE epsilon4 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).


CONCLUSIONS
COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon4 allele that proves greater in women with AD.
Martínez
Manuel Fernández
MF
Neurology Department, Hospital de Cruces, Baracaldo, Vizcaya, Spain. mfernandezm@meditex.es
Martín
Xabier Elcoroaristizabal
XE
Alcelay
Luís Galdos
LG
Flores
Jessica Castro
JC
Valiente
Juan María Uterga
JM
Juanbeltz
Begoña Indakoetxea
BI
Beldarraín
María Angeles Gómez
MA
López
Josefa Moraza
JM
Gonzalez-Fernández
María Carmen
MC
Salazar
Ana Molano
AM
Gandarias
Rocio Bereincua
RB
Borda
Sandra Inglés
SI
Marqués
Nuria Ortiz
NO
Amillano
Miryam Barandiarán
MB
Zabaleta
María Carrasco
MC
de Pancorbo
Marian M
MM
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D003430:Cross-Sectional Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012737:Sex Factors
D053327:Apolipoprotein E4; D002394:Catechol O-Methyltransferase