title: ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.
abstract: 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.
authors: 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
authors: Mari
authors: M
authors: Levula
authors: Nina
authors: N
authors: Airla
authors: Niku
authors: N
authors: Oksala
authors: Jussi A
authors: JA
authors: Hernesniemi
authors: Markku
authors: M
authors: Pelto-Huikko
authors: Juha-Pekka
authors: JP
authors: Salenius
authors: Rainer
authors: R
authors: Zeitlin
authors: Otso
authors: O
authors: Järvinen
authors: Ari-Pekka J
authors: AP
authors: Huovila
authors: Seppo T
authors: ST
authors: Nikkari
authors: Olli
authors: O
authors: Jaakkola
authors: Erkki
authors: E
authors: Ilveskoski
authors: Jussi
authors: J
authors: Mikkelsson
authors: Markus
authors: M
authors: Perola
authors: Reijo
authors: R
authors: Laaksonen
authors: Leena
authors: L
authors: Kytömäki
authors: Juhani T
authors: JT
authors: Soini
authors: Mika
authors: M
authors: Kähönen
authors: Jyrki
authors: J
authors: Parkkinen
authors: Pekka J
authors: PJ
authors: Karhunen
authors: Terho
authors: T
authors: Lehtimäki
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C068490:ADAM8 protein, human