title: Common variation in the ADAM8 gene affects serum sADAM8 concentrations and the risk of myocardial infarction in two independent cohorts.
abstract: OBJECTIVE
  The single nucleotide polymorphism (SNP) rs2995300 in the metalloproteinase-disintegrin gene ADAM8 has been shown to affect the areas of complicated coronary plaques and the risk of fatal myocardial infarction (MI) in men. This study was set up to further investigate the role of ADAM8 in MI.
  
  
  OBJECTIVE
  To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk.
  
  
  METHODS
  Samples from the Finnish cardiovascular study (FINCAVAS, N=2156) and the angiography and genes study (ANGES, N=1000) were genotyped. Serum sADAM8 concentrations were determined with ELISA (N=443). ADAM8 mRNA levels in atherosclerotic plaques were analysed from the tampere vascular study (TVS, N=53) samples.
  
  
  RESULTS
  A significantly increased MI risk for carriers of the rs2995300C allele and the rs2275725 A allele was revealed in the meta-analysis of the ANGES and FINCAVAS patient data (OR=1.42, P<0.001 and OR=1.43, P<0.001). The risk increase was comparable to that caused by smoking in these cohorts. The risk allele carriers also had higher sADAM8 serum concentrations.
  
  
  CONCLUSIONS
  The risk alleles of the investigated ADAM8 SNPs were associated with elevated sADAM8 serum levels and MI risk. The present results implicate ADAM8 in the development of CVDs and suggest its prognostic and therapeutic potential.
authors.affiliation: Department of Clinical Chemistry, Tampere University Hospital and Medical School at University of Tampere, Tampere, Finland. emma.raitoharju@uta.fi
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.forename: Mari
authors.initials: M
authors.lastname: Levula
authors.forename: Pekka
authors.initials: P
authors.lastname: Kuukasjärvi
authors.forename: Jari
authors.initials: J
authors.lastname: Laurikka
authors.forename: Kjell
authors.initials: K
authors.lastname: Nikus
authors.forename: Ari-Pekka J
authors.initials: AP
authors.lastname: Huovila
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
authors.forename: Jari
authors.initials: J
authors.lastname: Viik
authors.forename: Rami
authors.initials: R
authors.lastname: Lehtinen
authors.forename: Markku
authors.initials: M
authors.lastname: Pelto-Huikko
authors.forename: Matti
authors.initials: M
authors.lastname: Tarkka
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000235:genetics*; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005387:Finland; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012306:Risk
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D051722:ADAM Proteins; C068490:ADAM8 protein, human