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Association between osteoprotegerin gene polymorphism and coronary artery disease in Japanese men

      Osteoprotegerin (OPG) is a member of TNF receptor family that regulates bone resorption as a decoy receptor for RANKL. Recently, high levels of OPG immunoreactivity and mRNA were demonstrated in human atherosclerotic lesions [
      • Schoppet M.
      • Al-Fakhri N.
      • Franke F.E.
      • et al.
      Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Monckeberg's sclerosis and atherosclerosis.
      ]. OPG was produced in vascular smooth muscle and endothelial cells [
      • Hofbauer L.C.
      • Shui C.
      • Riggs B.L.
      • et al.
      Effects of immunosuppressants on receptor activator of NF-kappaB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells.
      ]. Serum OPG levels were associated with the severity of coronary artery disease (CAD) [
      • Jono S.
      • Ikari Y.
      • Shioi A.
      • et al.
      Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease.
      ,
      • Schoppet M.
      • Sattler A.M.
      • Schaefer J.R.
      • et al.
      Increased osteoprotegerin serum levels in men with coronary artery disease.
      ], carotid atherosclerosis [
      • Kiechl S.
      • Schett G.
      • Wenning G.
      • et al.
      Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease.
      ], and peripheral artery disease [
      • Ziegler S.
      • Kudlacek S.
      • Luger A.
      • Minar E.
      Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease.
      ]. In contrast, serum levels of TRIAL, the second ligand for OPG, were low in patients with CAD, especially in those with acute coronary syndrome (ACS) [
      • Schoppet M.
      • Sattler A.M.
      • Schaefer J.R.
      • Hofbauer L.C.
      Osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in atherosclerosis.
      ]. OPG/TRAIL may play a role in the development of atherosclerotic disease. Recently, OPG gene polymorphism (T-to-C at 950) was reported to be associated with carotid intima-media thickness (IMT) and post-ischemic forearm blood flow [
      • Brandstrom H
      • Stiger F
      • Lind L.
      • et al.
      A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function.
      ]. Patients with C/C genotype had increased IMT and decreased blood flow compared with C/T or T/T. This polymorphism was associated with serum OPG levels, which were highest with C/C genotype [
      • Soufi M.
      • Schoppet M.
      • Sattler A.M.
      • et al.
      Osteoprotegerin gene polymorphisms in men with coronary artery disease.
      ].

      Keywords

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