Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns.
Polymorphisms affecting the expression of matrix metalloproteinases (MMPs), i.e. proteolytic enzymes that degrade intercellular material, have been found at position -1607 (1G/2G) in MMP1 and at -1171 (5A/6A) in MMP3. Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer's disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson's disease (PD) patients, suggesting a role for MMPs in these disorders. The aim was to investigate a possible association between the afore-mentioned MMP1 and MMP3 polymorphisms and the risk of developing AD or PD. The polymorphisms were genotyped in 97 AD, 52 PD and 101 control patients. We found an interaction between MMP3*5A and APOE 4 alleles (P < 0.0001) which increases the risk of AD (OR: 23.7, 95% CI: 5.8-144.9, P < 0.0001) compared to those who possess neither MMP3*5A nor APOE 4. In conclusion, our finding suggests that the MMP3 gene, especially together with APOE 4, may contribute to the development of AD.
Saarela
Marika S
MS
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Center for Laboratory Medicine, Tampere University Hospital, PO Box 2000, FIN-33521, Finland. masusaar@cc.jyu.fi
Lehtimäki
Terho
T
Rinne
Juha O
JO
Hervonen
Antti
A
Jylhä
Marja
M
Röyttä
Matias
M
Ahonen
Jukka-Pekka
JP
Mattila
Kari M
KM
D000368:Aged; D000369:Aged, 80 and over; D000409:Alanine / Q000235:genetics; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D012306:Risk
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D000409:Alanine