Department of Clinical Chemistry, Tampere University Hospital and Medical School at University of Tampere, Tampere, Finland.
Atherosclerosis. 2011 Sep;218(1):127-33. doi: 10.1016/j.atherosclerosis.2011.05.005. Epub 2011 May 13.
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.
To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk.
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.
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.
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.
金属蛋白酶-解聚素基因 ADAM8 中的单核苷酸多态性 (SNP) rs2995300 已被证明会影响复杂冠状动脉斑块的面积和男性致命性心肌梗死 (MI) 的风险。本研究旨在进一步研究 ADAM8 在 MI 中的作用。
研究 ADAM8 SNP rs2995300 和 rs2275725 与 ADAM8 mRNA 水平、血清可溶性 ADAM8(sADAM8)浓度和 MI 风险的可能关联。
对芬兰心血管研究 (FINCAVAS，N=2156) 和血管造影和基因研究 (ANGES，N=1000) 的样本进行基因分型。用 ELISA 法测定血清 sADAM8 浓度 (N=443)。从坦佩雷血管研究 (TVS，N=53) 样本中分析动脉粥样硬化斑块中的 ADAM8 mRNA 水平。
在 ANGES 和 FINCAVAS 患者数据的荟萃分析中，rs2995300C 等位基因和 rs2275725A 等位基因携带者的 MI 风险显著增加 (OR=1.42，P<0.001 和 OR=1.43，P<0.001)。在这些队列中，风险等位基因携带者的吸烟风险也增加了。风险等位基因携带者的血清 sADAM8 浓度也较高。
所研究的 ADAM8 SNP 的风险等位基因与升高的 sADAM8 血清水平和 MI 风险相关。本研究结果提示 ADAM8 参与 CVD 的发生发展，并提示其具有预后和治疗潜力。
