Fetuin-A (AHSG) Human ELISA

Summary

Fetuin-A (AHSG), a 59 kDa glycoprotein, consisting of two cystatin-like domains and a smaller unrelated domain, is predominantly synthesized in liver. It is secreted into the blood stream and deposited as a noncollagenous protein in mineralized bones and teeth. Fetuin-A occurs in high serum concentrations during foetal life, whereas its level declines following infection, inflamatory and malignancy. Fetuin-A acts as an important circulating inhibitor of ectopic calcification, frequent complication of many degenerative diseases. Low serum level of Fetuin-A is associated with vascular and valvular calcification, atherosclerosis, malnutrition and higher cardiovascular mortality in chronic renal failure, liver cancer and liver cirrhosis patients on long-term dialysis. AHSG protein represents a natural inhibitor of tyrosinase kinase activity of the insulin receptor. It may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation. The serum and bone-resident Fetuin-A binds to transforming growth factor-β and blocks TGF-β binding to cell surface receptors.

Features

• The total assay time is less than 3 hours.
• The kit measures serum or plasma Fetuin-A.
• Calibrator is human plasma based.
• Quality Controls are human serum based.
• Components of the kit are provided ready-to-use, concentrated and lyophilized.

Research topic

Bone and cartilage metabolism, Renal disease

Assay format

Sandwich ELISA, HRP-labelled antibody

Applications

Plasma-Citrate, Plasma-EDTA, Plasma-Heparin, Serum

Sample requirements

10 µl/well

Storage/Shipping

Store the kit at 2–8°C. Under these conditions, the kit is stable until the expiration date (see label on the box).

Calibration Curve

Calibration range

2 – 100 ng/ml

Limit of detection

Analytical Limit of Detection is calculated from the real Fetuin-A values in wells and is 0.35 ng/ml

Intra-assay (Within-Run, n=8)

CV = 3.5 %

Inter-assay (Run-to-Run, n=5)

CV = 5.4 %

Spiking Recovery

102.8 %

Dilution Linearity

95.9 %

Cross-Reactivity

References to this product

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• Brix JM, Stingl H, Hollerl F, Schernthaner GH, Kopp HP, Schernthaner G. Elevated Fetuin-A concentrations in morbid obesity decrease after dramatic weight loss. J Clin Endocrinol Metab. 2010 Nov;95 (11):4877-81
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• Caglar K, Yilmaz MI, Saglam M, Cakir E, Kilic S, Sonmez A, Eyileten T, Yenicesu M, Oguz Y, Tasar M, Vural A, Ikizler TA, Stenvinkel P, Lindholm B. Serum fetuin-a concentration and endothelial dysfunction in chronic kidney disease. Nephron Clin Pract. 2008;108 (3):c233-40
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• Ford ML, Tomlinson LA, Smith ER, Rajkumar C, Holt SG. Fetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stages 3 and 4. Nephrol Dial Transplant. 2010 Jan 14;
• Hennige AM, Staiger H, Wicke C, Machicao F, Fritsche A, Haring HU, Stefan N. Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS One. 2008;3 (3):e1765
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• Kaden JJ, Reinohl JO, Blesch B, Brueckmann M, Haghi D, Borggrefe M, Schmitz F, Klomfass S, Pillich M, Ortlepp JR. Systemic and local levels of fetuin-A in calcific aortic valve stenosis. Int J Mol Med. 2007 Aug;20 (2):193-7
• Kamel AA, El-Attar HA, Abaza MM, Gaber EW, Badawi SS. Study of serum osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and fetuin-A in patients with chronic renal failure. Bull. Alex. Fac. Med. 2007;43 (3)
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• Lorant DP, Grujicic M, Hoebaus C, Brix JM, Hoellerl F, Schernthaner G, Koppensteiner R, Schernthaner GH. Fetuin-A levels are increased in patients with type 2 diabetes and peripheral arterial disease. Diabetes Care. 2011 Jan;34 (1):156-61
• Mori K, Emoto M, Araki T, Yokoyama H, Teramura M, Lee E, Motoyama K, Koyama H, Shoji T, Inaba M, Nishizawa Y. Association of serum fetuin-A with carotid arterial stiffness. Clin Endocrinol (Oxf) . Feb;66(2):246-50 (2007)
• Mori K, Emoto M, Yokoyama H, Araki T, Teramura M, Koyama H, Shoji T, Inaba M, Nishizawa Y. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care . Feb;29(2):468 (2006)
• Oikawa O, Higuchi T, Yamazaki T, Yamamoto C, Fukuda N, Matsumoto K. Evaluation of serum fetuin-A relationships with biochemical parameters in patients on hemodialysis. Clin Exp Nephrol. 2007 Dec;11 (4):304-8
• Panczyk-Tomaszewska M, Skrzypczyk P, Ziolkowska H, Adamczuk D, Roszkowska-Blaim M. [Fetuin A in children with nephrotic syndrome]. Pol Merkur Lekarski. 2008;24 Suppl 4:65-7
• Pertosa G, Simone S, Ciccone M, Porreca S, Zaza G, Dalfino G, Memoli B, Procino A, Bonomini M, Sirolli V, Castellano G, Gesualdo L, Ktena M, Schena FP, Grandaliano G. Serum fetuin a in hemodialysis: a link between derangement of calcium-phosphorus homeostasis and progression of atherosclerosis?. Am J Kidney Dis. 2009 Mar;53 (3):467-74
• Petrik V, Saadoun S, Loosemore A, Hobbs J, Opstad KS, Sheldon J, Tarelli E, Howe FA, Bell BA, Papadopoulos MC. Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma. Clin Chem. 2008 Apr;54 (4):713-22
• Roos M, Richart T, Kouznetsova T, von Eynatten M, Lutz J, Heemann U, Baumann M, Staessen JA. Fetuin-A and arterial stiffness in patients with normal kidney function. Regul Pept. 2009 Apr 10;154 (1-3):39-43
• Sigrist MK, Levin A, Er L, McIntyre CW. Elevated osteoprotegerin is associated with all-cause mortality in CKD stage 4 and 5 patients in addition to vascular calcification. Nephrol Dial Transplant. 2009 Oct;24 (10):3157-62
• Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol. 2007 Nov;2 (6):1241-8
• Smith ER, Ford ML, Tomlinson LA, Rocks BF, Rajkumar C, Holt SG. Poor agreement between commercial ELISAs for plasma fetuin-A: an effect of protein glycosylation?. Clin Chim Acta. 2010 Apr 25;
• Stefan N, Hennige AM, Staiger H, Machann J, Schick F, Krober SM, Machicao F, Fritsche A, Haring HU. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care . Apr;29(4):853-7 (2006)
• Stejskal D, Karpisek M, Vrtal R, Student V, Solichova P, Fiala R, Stejskal P. Urine fetuin-A values in relation to the presence of urolithiasis. BJU Int. 2008 May;101 (9):1151-4
• Tonjes A, Fasshauer M, Kratzsch J, Stumvoll M, Bluher M. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes. PLoS One. 2010;5 (11):e13911
• Tumani H, Lehmensiek V, Rau D, Guttmann I, Tauscher G, Mogel H, Palm C, Hirt V, Suessmuth SD, Sapunova-Meier I, Ludolph AC, Brettschneider J. CSF proteome analysis in clinically isolated syndrome (CIS): candidate markers for conversion to definite multiple sclerosis. Neurosci Lett. 2009 Mar 13;452 (2):214-7
• Urbanova M, Kalousova M, Zima T, Skibova J, Wohlfahrt P, Viklicky O. Fetuin-A early after renal transplantation. Kidney Blood Press Res. 2009;32 (3):217-22
• Uz O, Kardesoglu E, Yiginer O, Bas S, Ipcioglu OM, Ozmen N, Aparci M, Cingozbay BY, Isilak Z, Cebeci BS. The relationship between coronary calcification and the metabolic markers of osteopontin, fetuin-A, and visfatin. Turk Kardiyol Dern Ars. 2009 Sep;37 (6):397-402
• Wojtysiak-Duma B, Duma D, Burska A, Janicki K, Zakaszewska K, Skałecki P, Janicka L, Solski J. Fetuin-A in patients undergoing peritoneal dialysis with coronary artery calcification. Annales Universitatis Marie Cu. XXI, N 1, 68, 2008
• Yang SJ, Hong HC, Choi HY, Yoo HJ, Cho GJ, Hwang TG, Baik SH, Choi DS, Kim SM, Choi KM. Effects of a three-month combined exercise programme on fibroblast growth factor 21 and fetuin-A levels and arterial stiffness in obese women. Clin Endocrinol (Oxf). 2011 Oct;75 (4):464-9
• Yilmaz MI, Saglam M, Qureshi AR, Carrero JJ, Caglar K, Eyileten T, Sonmez A, Cakir E, Oguz Y, Vural A, Yenicesu M, Stenvinkel P, Lindholm B, Axelsson J. Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin. Nephrol Dial Transplant. 2008 May;23 (5):1621-7
• Ziolkowska H, Brzewski M, Roszkowska-Blaim M. Determinants of the intima-media thickness in children and adolescents with chronic kidney disease. Pediatr Nephrol. 2008 May;23 (5):805-11
• Ziolkowska H, Wojnar J, Panczyk-Tomaszewska M, Roszkowska-Blaim M. [Fetuin A in children with renal diseases]. Przegl Lek. 2006;63 Suppl 3:54-6

References to summary

• Lebreton J.P., Joisel F., Raoult J.P., Lannuzel B., Rogez J.P., Humbert G.: Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. J Clin Invest 1979; 64: 1118–1129
• Schinke T., Amendt C., Trindl A., Poeschke O., Mueller-Esterl W., Jahnen-Dechent W.: The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 1996; 271: 20789–96
• Osawa M., Umetsu K., Sato M., Ohki T., Yukawa N., Suzuki T., Takeichi S.: Structure of the gene encoding human alpha 2-HS glycoprotein. Gene 1997; 196: 121–125
• Mathews S. T., Chellam N., Srinivas P. R., Cintron V. J., Leon M. A., Goustin A. S., Grungerger G.: Alpha2-HSG, a specific inhibitor of insulin receptor autophosphory­lation, interacts with the insulin receptor. Moll Cell Endocrinol 2000; 164: 87–98
• Heiss A., DuChesne A., Denecke B., Grotzinger J., Yamamoto K., Renne T., Jahnen-Dechent W.: Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A: formation of colloidal calciprotein particles. J Biol Chem 2003; 278: 13333–13341
• Ketteler M., Bongartz P., Westenfeld R., Ernst Wildberger J., Horst Mahnken A., Boehm R., Metzger T., Wanner C., Jahnen-Dechent W., Floege J.: Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003; 361: 827–833
• Schafer C., Heiss A., Schwarz A., Westenfeld R., Ketteler M., Floege J., Muller-Esterl W., Schinke T., Jahnen-Dechent W.: 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
• Puchades M., Hansson S.F., Nilsson C.L., Andreasen N., Blennow K., Davidsson P.: Proteomic studies of potential cerebrospinal fluid protein markers for Alzheimer's di­sease. Brain Res Mol Brain Res 2003; 118: 140–146
• Kwak J.Y., Ma T.Z., Yoo M.J., Hee Choi B., Kim H.G., Kim S.R., Yim C.Y., Kwak Y.G.: The comparative analysis of serum proteomes for the discovery of biomarkers for acute myeloid leukemia. Exp Hematol 2004; 32: 836–842
• Floege J., Ketteler M.: Vascular calcification in patients with end-stage renal disease. Nephrol Dial Transplant. 2004; 19 Suppl 5: V59–66. Review
• Wang A.Y., Woo J., Lam C.W., Wang M., Chan I.H., Gao P., Liu S.F., Li P.K., Sanderson J.E.: Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005; 20: 1676–1685
• Osawa M., Tian W., Horiuchi H., Kaneko M., Umetsu K.: Association of alpha2-HS glycoprotein (AHSG, fetuin-A) polymorphism with AHSG and phosphate serum levels. Hum Genet 2005; 116: 146–151
• Mehrotra R., Westenfeld R., Christenson P., Budoff M., Ipp E., Takasu J., Gupta A., Norris K., Ketteler M., Adler S.: Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification. Kidney Int 2005; 67: 1070–1077
• Kundranda M.N., Henderson M., carter K.J., Gorden L., Binhazim A., Ray S., Baptiste T., Shokrani M., Leite-Browning M.L., Jahnen-Dechent W., Matrisian L.M. Ochieng J.: The serum glycoprotein fetuin-A promotes Lewis lung carcinoma tumorigenesis via adhesive-dependent and adhesiveindependent mechanisms. Cancer Res 2005; 65: 499–506 Human Fetuin-A ELISA (page 24 of 28) VERSION: 33 290807 07
• Geroldi D., Minoretti P., Bianchi M., Di Vito C. Reino M., Bertona M., Emanuele E.: Genetic association of alpha2-Heremans-Schmid glycoprotein polymorphism with late-onset Alzheimer's disease in Italians. Neurosci Lett 2005; 386: 176–178
• Reynolds J.L., Skepper J.N., McNair R., Kasama T., Gupta K., Wissberg P.L., Jahnen-Dechent W., Shanahan C.M.: Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 2005; 16: 2920–2930
• Ix J.H., Shilipak M.G., Brandenburg V.M., Ali S., Ketteler M., Whooley M.A.: Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006; 113: 1760–1767
• Zhou H., Pisitkun T., Aponte A., Yuen P.S., Hoffert J.D., Yasuda H., Hu X., Chawla L., Shen R.F., Knepper M.A., Star R.A.: Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. Kidney Int 2006; 70: 1847–1857

By research topic:

• Bone and cartilage metabolism
• Renal disease

By molecule:

• Fetuin-A

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