View More View Less
  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar Családorvosi Tanszék Budapest Kútvölgyi út 4. 1125
  • 2 Semmelweis Egyetem, Általános Orvostudományi Kar Népegészségtani Intézet Budapest
Open access

A máj által termelt fetuin-A (eredeti nevén α2-Heremans–Schmid-glikoprotein) szerteágazó funkciókkal bíró molekula. Bár negatív akutfázis-fehérje, szerepe a szubklinikus gyulladásban vitatott. Gátolja az inzulinreceptor autofoszforilációját, szérumkoncentrációja korrelál az inzulinrezisztenciával. A zsírsejtek működészavarát okozza. Szérumszintje összefügg az elhízással és a nem alkoholos zsírmájbetegséggel. Bár ezen tulajdonságai alapján azt várnánk, hogy az atherosclerosis progresszióját segíti, cardiovascularis betegségekben játszott szerepe ennél összetettebb. A fetuin-A a szöveti és a vascularis kalcifikáció természetes gátlómolekulájaként az atherosclerosisban védő szerepet tölt be. A szerzők a fetuin-A artériakalcifikációban és cardiovascularis betegségekben betöltött szerepét és prognosztikai értékét tekintik át, kitérve az ellentmondásosnak tűnő irodalmi eredmények magyarázatára és a lehetséges jövőbeni kutatási irányokra is. Orv. Hetil., 2014, 155(1), 16–23.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Rizzu, P., Baldini, A.: Three members of the human cystatin gene superfamily, AHSG, HRG, and KNG, map within one megabase of genomic DNA at 3q27. Cytogenet. Cell Genet., 1995, 70, 26–28.

    Baldini A. , 'Three members of the human cystatin gene superfamily, AHSG, HRG, and KNG, map within one megabase of genomic DNA at 3q27 ' (1995 ) 70 Cytogenet. Cell Genet. : 26 -28.

    • Search Google Scholar
  • Kalabay, L., Szalay, F., Nemesánszky, E., et al.: Decreased serum alfa2-HS-glycoprotein concentration in patients with primary biliary cirrhosis. J. Hepatol., 1997, 26, 1426–1427.

    Nemesánszky E. , 'Decreased serum alfa2-HS-glycoprotein concentration in patients with primary biliary cirrhosis ' (1997 ) 26 J. Hepatol. : 1426 -1427.

    • Search Google Scholar
  • Kalabay, L., Gráf, L., Vörös, K., et al.: Human serum fetuin A/alpha 2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores. BMC Gastroenterol., 2007, 7, 15.

    Vörös K. , 'Human serum fetuin A/alpha 2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores ' (2007 ) 7 BMC Gastroenterol. : 15 -.

    • Search Google Scholar
  • Mori, K., Emoto, M., Inaba, M.: Fetuin-A: A multifunctional protein. Recent Pat. Endocr. Metab. Immune Drug Discov., 2011, 5, 124–146.

    Inaba M. , 'Fetuin-A: A multifunctional protein ' (2011 ) 5 Recent Pat. Endocr. Metab. Immune Drug Discov. : 124 -146.

    • Search Google Scholar
  • Daveau, M., Davrinche, C., Julen, N., et al.: The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines in hepatoma HepG2 cells. FEBS Lett., 1988, 241, 191–194.

    Julen N. , 'The synthesis of human alpha-2-HS glycoprotein is down-regulated by cytokines in hepatoma HepG2 cells ' (1988 ) 241 FEBS Lett. : 191 -194.

    • Search Google Scholar
  • Hennige, A. M., Staiger, H., Wicke, C., et al.: Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One, 2008, 3, e1765.

    Wicke C. , 'Fetuin-A induces cytokine expression and suppresses adiponectin production ' (2008 ) 3 PLoS One : e1765 -.

    • Search Google Scholar
  • Dasgupta, S., Bhattacharya, S., Biswas, A., et al.: NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem. J., 2010, 429, 451–462.

    Biswas A. , 'NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance ' (2010 ) 429 Biochem. J. : 451 -462.

    • Search Google Scholar
  • Kaess, B. M., Enserro, D. M., McManus, D. D., et al.: Cardiometabolic correlates and heritability of fetuin-A, retinol-binding protein 4, and fatty-acid binding protein 4 in the Framingham Heart Study. J. Clin. Endocrinol. Metab., 2012, 97, E1943–E1947.

    McManus D. D. , 'Cardiometabolic correlates and heritability of fetuin-A, retinol-binding protein 4, and fatty-acid binding protein 4 in the Framingham Heart Study ' (2012 ) 97 J. Clin. Endocrinol. Metab. : E1943 -E1947.

    • Search Google Scholar
  • Vörös, K., Gráf, L. Jr., Prohászka, Z., et al.: Serum fetuin-A in metabolic and inflammatory pathways in patients with myocardial infarction. Eur. J. Clin. Invest., 2011, 41, 703–709.

    Prohászka Z. , 'Serum fetuin-A in metabolic and inflammatory pathways in patients with myocardial infarction ' (2011 ) 41 Eur. J. Clin. Invest. : 703 -709.

    • Search Google Scholar
  • Srinivas, P. R., Wagner, A. S., Reddy, L. V., et al.: Serum alpha(2)-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol. Endocrinol., 1993, 7, 1445–1455.

    Reddy L. V. , 'Serum alpha(2)-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level ' (1993 ) 7 Mol. Endocrinol. : 1445 -1455.

    • Search Google Scholar
  • Kalabay, L., Chavin, K., Lebreton, J. P., et al.: Human recombinant alpha 2-HS glycoprotein is produced in insect cells as a full length inhibitor of the insulin receptor tyrosine kinase. Horm. Metab. Res., 1998, 30, 1–6.

    Lebreton J. P. , 'Human recombinant alpha 2-HS glycoprotein is produced in insect cells as a full length inhibitor of the insulin receptor tyrosine kinase ' (1998 ) 30 Horm. Metab. Res. : 1 -6.

    • Search Google Scholar
  • Ix, J. H., Sharma, K.: Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J. Am. Soc. Nephrol., 2010, 21, 406–412.

    Sharma K. , 'Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK ' (2010 ) 21 J. Am. Soc. Nephrol. : 406 -412.

    • Search Google Scholar
  • Kahraman, A., Sowa, J. P., Schlattjan, M., et al.: Fetuin-A mRNA expression is elevated in NASH compared with NAFL patients. Clin. Sci. (Lond.), 2013, 125, 391–400.

    Schlattjan M. , 'Fetuin-A mRNA expression is elevated in NASH compared with NAFL patients ' (2013 ) 125 Clin. Sci. (Lond.) : 391 -400.

    • Search Google Scholar
  • Stefan, N., Hennige, A. M., Staiger, H., et al.: Alpha2-Heremans–Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care, 2006, 29, 853–857.

    Staiger H. , 'Alpha2-Heremans–Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans ' (2006 ) 29 Diabetes Care : 853 -857.

    • Search Google Scholar
  • Pal, D., Dasgupta, S., Kundu, R., et al.: Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nat. Med., 2012, 18, 1279–1285.

    Kundu R. , 'Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance ' (2012 ) 18 Nat. Med. : 1279 -1285.

    • Search Google Scholar
  • Stefan, N., Häring, H. U.: Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans. Nat. Med., 2013, 19, 394–395.

    Häring H. U. , 'Circulating fetuin-A and free fatty acids interact to predict insulin resistance in humans ' (2013 ) 19 Nat. Med. : 394 -395.

    • Search Google Scholar
  • Lin, X., Braymer, H. D., Bray, G. A., et al.: Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity. Life Sci., 1998, 63, 145–153.

    Bray G. A. , 'Differential expression of insulin receptor tyrosine kinase inhibitor (fetuin) gene in a model of diet-induced obesity ' (1998 ) 63 Life Sci. : 145 -153.

    • Search Google Scholar
  • Mathews, S. T., Singh, G. P., Ranalletta, M., et al.: Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes, 2002, 51, 2450–2458.

    Ranalletta M. , 'Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene ' (2002 ) 51 Diabetes : 2450 -2458.

    • Search Google Scholar
  • Ix, J. H., Wassel, C. L., Kanaya, A. M. et al.: Fetuin-A and incident diabetes mellitus in older persons. JAMA, 2008, 300, 182–188.

    Kanaya A. M. , 'Fetuin-A and incident diabetes mellitus in older persons ' (2008 ) 300 JAMA : 182 -188.

    • Search Google Scholar
  • Ix, J. H., Shlipak, M. G., Brandenburg, V. M., et al.: Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation, 2006, 113, 1760–1767.

    Brandenburg V. M. , 'Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study ' (2006 ) 113 Circulation : 1760 -1767.

    • Search Google Scholar
  • Haukeland, J. W., Dahl, T. B., Yndestad, A., et al.: Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur. J. Endocrinol., 2012, 166, 503–510.

    Yndestad A. , 'Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies ' (2012 ) 166 Eur. J. Endocrinol. : 503 -510.

    • Search Google Scholar
  • Xu, Y., Xu, M., Bi, Y., et al.: Serum fetuin-A is correlated with metabolic syndrome in middle-aged and elderly Chinese. Atherosclerosis, 2011, 216, 180–186.

    Bi Y. , 'Serum fetuin-A is correlated with metabolic syndrome in middle-aged and elderly Chinese ' (2011 ) 216 Atherosclerosis : 180 -186.

    • Search Google Scholar
  • Ou, H. Y., Yang, Y. C., Wu, H. T., et al.: Serum fetuin-A concentrations are elevated in subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes. Clin. Endocrinol. (Oxf.), 2011, 75, 450–455.

    Wu H. T. , 'Serum fetuin-A concentrations are elevated in subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes ' (2011 ) 75 Clin. Endocrinol. (Oxf.) : 450 -455.

    • Search Google Scholar
  • Mori, K., Emoto, M., Yokoyama, H., et al.: Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care, 2006, 29, 468.

    Yokoyama H. , 'Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects ' (2006 ) 29 Diabetes Care : 468 -.

    • Search Google Scholar
  • Stefan, N., Häring, H. U., Schulze, M. B.: Association of fetuin-A level and diabetes risk. JAMA, 2008, 300, 2247–2248.

    Schulze M. B. , 'Association of fetuin-A level and diabetes risk ' (2008 ) 300 JAMA : 2247 -2248.

    • Search Google Scholar
  • Jensen, M. K., Bartz, T. M., Djoussé, L., et al.: Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study. Diabetes Care, 2013, 36, 3121–3127.

    Djoussé L. , 'Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study ' (2013 ) 36 Diabetes Care : 3121 -3127.

    • Search Google Scholar
  • Schäfer, C., Heiss, A., Schwarz, A., et al.: The serum protein alpha(2)-Heremans–Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J. Clin. Invest., 2003, 112, 357–366.

    Schwarz A. , 'The serum protein alpha(2)-Heremans–Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification ' (2003 ) 112 J. Clin. Invest. : 357 -366.

    • Search Google Scholar
  • Heiss, A., DuChesne, A., Denecke, B., et al.: Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J. Biol. Chem., 2003, 278, 13333–13341.

    Denecke B. , 'Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles ' (2003 ) 278 J. Biol. Chem. : 13333 -13341.

    • Search Google Scholar
  • Mori, K., Emoto, M., Araki, T., et al.: Association of serum fetuin-A with carotid arterial stiffness. Clin. Endocrinol. (Oxf.), 2007, 66, 246–250.

    Araki T. , 'Association of serum fetuin-A with carotid arterial stiffness ' (2007 ) 66 Clin. Endocrinol. (Oxf.) : 246 -250.

    • Search Google Scholar
  • Dogru, T., Genc, H., Tapan, S., et al.: Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease. Clin. Endocrinol. (Oxf.), 2013, 78, 712–717.

    Tapan S. , 'Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease ' (2013 ) 78 Clin. Endocrinol. (Oxf.) : 712 -717.

    • Search Google Scholar
  • Fiore, C. E., Celotta, G., Politi, G. G., et al.: Association of high alpha2-Heremans–Schmid glycoprotein/fetuin concentration in serum and intima-media thickness in patients with atherosclerotic vascular disease and low bone mass. Atherosclerosis, 2007, 195, 110–115.

    Politi G. G. , 'Association of high alpha2-Heremans–Schmid glycoprotein/fetuin concentration in serum and intima-media thickness in patients with atherosclerotic vascular disease and low bone mass ' (2007 ) 195 Atherosclerosis : 110 -115.

    • Search Google Scholar
  • Rittig, K., Thamer, C., Haupt, A., et al.: High plasma fetuin-A is associated with increased carotid intima-media thickness in a middle-aged population. Atherosclerosis, 2009, 207, 341–342.

    Haupt A. , 'High plasma fetuin-A is associated with increased carotid intima-media thickness in a middle-aged population ' (2009 ) 207 Atherosclerosis : 341 -342.

    • Search Google Scholar
  • Westenfeld, R., Schäfer, C., Krüger, T., et al.: Fetuin-A protects against atherosclerotic calcification in CKD. J. Am. Soc. Nephrol., 2009, 20, 1264–1274.

    Krüger T. , 'Fetuin-A protects against atherosclerotic calcification in CKD ' (2009 ) 20 J. Am. Soc. Nephrol. : 1264 -1274.

    • Search Google Scholar
  • Mori, K., Ikari, Y., Jono, S., et al.: Fetuin-A is associated with calcified coronary artery disease. Coron. Artery Dis., 2010, 21, 281–285.

    Jono S. , 'Fetuin-A is associated with calcified coronary artery disease ' (2010 ) 21 Coron. Artery Dis. : 281 -285.

    • Search Google Scholar
  • Emoto, M., Mori, K., Lee, E., et al.: Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus. Metabolism, 2010, 59, 873–878.

    Lee E. , 'Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus ' (2010 ) 59 Metabolism : 873 -878.

    • Search Google Scholar
  • Mehrotra, R., Westenfeld, R., Christenson, P., et al.: Serum fetuin-A in nondialyzed patients with diabetic nephropathy: Relationship with coronary artery calcification. Kidney Int., 2005, 67, 1070–1077.

    Christenson P. , 'Serum fetuin-A in nondialyzed patients with diabetic nephropathy: Relationship with coronary artery calcification ' (2005 ) 67 Kidney Int. : 1070 -1077.

    • Search Google Scholar
  • Ix, J. H., Barrett-Connor, E., Wassel, C. L., et al.: The associations of fetuin-A with subclinical cardiovascular disease in community-dwelling persons: the Rancho Bernardo Study. J. Am. Coll. Cardiol., 2011, 58, 2372–2379.

    Wassel C. L. , 'The associations of fetuin-A with subclinical cardiovascular disease in community-dwelling persons: the Rancho Bernardo Study ' (2011 ) 58 J. Am. Coll. Cardiol. : 2372 -2379.

    • Search Google Scholar
  • Ix, J. H., Katz, R., De Boer, I. H., et al.: Fetuin-A is inversely associated with coronary artery calcification in community-living persons: the Multi-Ethnic Study of Atherosclerosis. Clin. Chem., 2012, 58, 887–895.

    Boer I. H. , 'Fetuin-A is inversely associated with coronary artery calcification in community-living persons: the Multi-Ethnic Study of Atherosclerosis ' (2012 ) 58 Clin. Chem. : 887 -895.

    • Search Google Scholar
  • Lorant, D. P., Grujicic, M., Hoebaus, C., et al.: Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes Care, 2011, 34, 156–161.

    Hoebaus C. , 'Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease ' (2011 ) 34 Diabetes Care : 156 -161.

    • Search Google Scholar
  • Erasom, L. H., Ginwala, N., Qasim, A. N., et al.: Association of lower plasma fetuin-A levels with peripheral arterial disease in type-2 diabetes. Diabetes Care, 2010, 33, 408–410.

    Qasim A. N. , 'Association of lower plasma fetuin-A levels with peripheral arterial disease in type-2 diabetes ' (2010 ) 33 Diabetes Care : 408 -410.

    • Search Google Scholar
  • Szeberin, Z., Fehérvári, M., Krepuska, M., et al.: Serum fetuin-A levels inversely correlate with the severity of arterial calcification in patients with chronic lower extremity atherosclerosis without renal disease. Int. Angiol., 2011, 30, 474–480.

    Krepuska M. , 'Serum fetuin-A levels inversely correlate with the severity of arterial calcification in patients with chronic lower extremity atherosclerosis without renal disease ' (2011 ) 30 Int. Angiol. : 474 -480.

    • Search Google Scholar
  • Fisher, E., Stefan, N., Saar, K., et al.: Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam Study. Circ. Cardiovasc. Genet., 2009, 2, 607–613.

    Saar K. , 'Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam Study ' (2009 ) 2 Circ. Cardiovasc. Genet. : 607 -613.

    • Search Google Scholar
  • Weikert, C., Stefan, N., Schulze, M. B., et al.: Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke. Circulation, 2008, 118, 2555–2562.

    Schulze M. B. , 'Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke ' (2008 ) 118 Circulation : 2555 -2562.

    • Search Google Scholar
  • Laughlin, G. A., Cummins, K. M., Wassel, C. L., et al.: The association of fetuin-A with cardiovascular disease mortality in older community-dwelling adults: The Rancho Bernardo Study. J. Am. Coll. Cardiol., 2012, 59, 1688–1696.

    Wassel C. L. , 'The association of fetuin-A with cardiovascular disease mortality in older community-dwelling adults: The Rancho Bernardo Study ' (2012 ) 59 J. Am. Coll. Cardiol. : 1688 -1696.

    • Search Google Scholar
  • Jensen, M. K., Bartz, T. M., Mukamal, K. J., et al.: Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: The cardiovascular health study. Diabetes Care, 2013, 36, 1222–1228.

    Mukamal K. J. , 'Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: The cardiovascular health study ' (2013 ) 36 Diabetes Care : 1222 -1228.

    • Search Google Scholar
  • Roos, M., von Eynatten, M., Heemann, U., et al.: Serum fetuin-A, cardiovascular risk factors, and six-year follow-up outcome in patients with coronary heart disease. Am. J. Cardiol., 2010, 105, 1666–1672.

    Heemann U. , 'Serum fetuin-A, cardiovascular risk factors, and six-year follow-up outcome in patients with coronary heart disease ' (2010 ) 105 Am. J. Cardiol. : 1666 -1672.

    • Search Google Scholar
  • Parker, B. D., Schurgers, L. J., Brandenburg, V. M. et al.: The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: The Heart and Soul Study. Ann. Intern. Med., 2010, 152, 640–648.

    Brandenburg V. M. , 'The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: The Heart and Soul Study ' (2010 ) 152 Ann. Intern. Med. : 640 -648.

    • Search Google Scholar
  • Mori, K., Emoto, M., Araki, T., et al.: Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus. Metabolism, 2008, 57, 1248–1252.

    Araki T. , 'Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus ' (2008 ) 57 Metabolism : 1248 -1252.

    • Search Google Scholar
  • Kaushik, S. V., Plaisance, E. P., Kim, T., et al.: Extended-release niacin decreases serum fetuin-A concentrations in individuals with metabolic syndrome. Diabetes Metab. Res. Rev., 2009, 25, 427–434.

    Kim T. , 'Extended-release niacin decreases serum fetuin-A concentrations in individuals with metabolic syndrome ' (2009 ) 25 Diabetes Metab. Res. Rev. : 427 -434.

    • Search Google Scholar
  • Smith, E. R., Ford, M L., Tomlinson, L. A., et al.: Poor agreement between commercial ELISAs for plasma fetuin-A: An effect of protein glycosylation? Clin. Chim. Acta, 2010, 411, 1367–1370.

    Tomlinson L. A. , 'Poor agreement between commercial ELISAs for plasma fetuin-A: An effect of protein glycosylation? ' (2010 ) 411 Clin. Chim. Acta : 1367 -1370.

    • Search Google Scholar