ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.
OBJECTIVE
Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.


METHODS
We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.


RESULTS
ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal pre-hospital MI (P=0.003) than did the TT homozygotes.


CONCLUSIONS
ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.
Levula
Mari
M
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland. mari.levula@uta.fi
Airla
Nina
N
Oksala
Niku
N
Hernesniemi
Jussi A
JA
Pelto-Huikko
Markku
M
Salenius
Juha-Pekka
JP
Zeitlin
Rainer
R
Järvinen
Otso
O
Huovila
Ari-Pekka J
AP
Nikkari
Seppo T
ST
Jaakkola
Olli
O
Ilveskoski
Erkki
E
Mikkelsson
Jussi
J
Perola
Markus
M
Laaksonen
Reijo
R
Kytömäki
Leena
L
Soini
Juhani T
JT
Kähönen
Mika
M
Parkkinen
Jyrki
J
Karhunen
Pekka J
PJ
Lehtimäki
Terho
T
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D003331:Coronary Vessels / Q000473:pathology; D005387:Finland / Q000453:epidemiology; D015870:Gene Expression; D006306:Health Surveys / Q000706:statistics & numerical data; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000235:genetics
D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C068490:ADAM8 protein, human