Analysis of functional polymorphisms of metalloproteinase genes in persons with vascular dementia and Alzheimer's disease.
BACKGROUND
Vascular dementia (VAD) and Alzheimer's disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia.


METHODS
This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied.


RESULTS
MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.4, OR = 1.7, 95% CI, 1.0-2.7, OR = 2.9, 95% CI, 1.5-5.9, and OR = 6.8, 95% CI, 1.3-35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) epsilon4 allele (OR = 6.0, 95% CI, 2.3-15.5, and OR = 14.3, 95% CI, 3.2-63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype.


CONCLUSIONS
Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease.
Flex
Andrea
A
Istituto di Medicina Interna e Geriatria, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, L.go A. Gemelli 8, 00168 Rome, Italy.
Gaetani
Eleonora
E
Proia
Anna S
AS
Pecorini
Giovanni
G
Straface
Giuseppe
G
Biscetti
Federico
F
Fioroni
Giuseppe
G
Sabusco
Alexandra
A
Flore
Roberto
R
Tondi
Paolo
P
Pola
Paolo
P
Pola
Roberto
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D003430:Cross-Sectional Studies; D015140:Dementia, Vascular / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D020782:Matrix Metalloproteinases