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Common variation in the ADAM8 gene affects serum sADAM8 concentrations and the risk of myocardial infarction in two independent cohorts.
Atherosclerosis 218, 127-133 (2011)
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 AIM: 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
ADAM8; Myocardial infarction; Polymorphisms; Soluble ADAM8; Atherosclerosis
ISSN (print) / ISBN
0021-9150
e-ISSN
1879-1484
Zeitschrift
Atherosclerosis
Quellenangaben
Band: 218,
Heft: 1,
Seiten: 127-133
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Research Unit Molecular Epidemiology (AME)