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.
Neurology Department, Hospital de Cruces, Baracaldo, Vizcaya, Spain. mfernandezm@meditex.es
Manuel Fernández
MF
Martínez
Xabier Elcoroaristizabal
XE
Martín
Luís Galdos
LG
Alcelay
Jessica Castro
JC
Flores
Juan María Uterga
JM
Valiente
Begoña Indakoetxea
BI
Juanbeltz
María Angeles Gómez
MA
Beldarraín
Josefa Moraza
JM
López
María Carmen
MC
Gonzalez-Fernández
Ana Molano
AM
Salazar
Rocio Bereincua
RB
Gandarias
Sandra Inglés
SI
Borda
Nuria Ortiz
NO
Marqués
Miryam Barandiarán
MB
Amillano
María Carrasco
MC
Zabaleta
Marian M
MM
de Pancorbo
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