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Fetuin-A is Associated to Serum Calcium and AHSG T256S Genotype but Not to Coronary Artery Calcification

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Abstract

Vascular calcification has been recently associated to an increased cardiovascular risk and mortality. In few studies, Fetuin-A showed an association to coronary artery calcification (CAC), although the physiopathological mechanism underlying this association has not been fully established yet. Seventy-four patients with one or more cardiovascular risk factor and asymptomatic for coronary vasculopathy were included in the study. CAC was evaluated by Agatston score. Serum Fetuin-A levels were determined by ELISA. Molecular analysis of AHSG T256S gene variant (rs4918) was performed by PCR–RFLP. Serum Fetuin-A was correlated to serum calcium (r = 0,321; P = 0,018), but not to serum phosphorous. Multivariate linear regression analysis confirmed this association and showed that calcium and AHSG genotype were independent predictors of Fetuin-A (P = 0.037, P = 0.014, respectively). In particular, subjects carrying the SS genotype had lower levels of Fetuin-A and calcium (P = 0.037 and P = 0.038, respectively). When we compare subjects with CAC 0–10 with subjects with CAC > 10, we found that only age and male gender (P < 0.001, P = 0.035, respectively), but not Fetuin-A, were associated to CAC. Fetuin-A is not associated to CAC in subjects with low cardiovascular risk profile and asymptomatic for coronary vasculopathy, suggesting that in this setting Fetuin-A, although correlated to serum levels of calcium, could be not involved in mineral deposition on coronary vessels.

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References

  • Bellia C, Tomaiuolo R, Caruso A et al (2012) Fetuin-A serum levels are not correlated to kidney function in long-lived subjects. Clin Biochem 45:637–640

    Article  CAS  PubMed  Google Scholar 

  • Bivona G, Bellia C, Caruso A et al (2008) Low serum Fetuin-A levels and cardiovascular events in end-stage renal disease [ESRD] patients. Res J Med Sci 2:200–202

    Google Scholar 

  • Budoff M, Young R, Lopez VA et al (2013) Progression of coronary calcium and incident coronary heart disease events: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol 61:1231–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai MM, Smith ER, Holt SG (2015) The role of Fetuin-A in mineral trafficking and deposition. Bonekey Rep 4:672. doi:10.1038/bonekey.2015.39.eCollection

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen NX, O’Neill KD, Chen X et al (2007) Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins. Am J Physiol Renal Physiol 292:F599–F606

    Article  CAS  PubMed  Google Scholar 

  • Ciaccio M, Bivona G, Di Sciacca R et al (2008) Changes in serum Fetuin-A and inflammatory markers levels in end-stage renal disease [ESRD]: effect of a single session hemodialysis. Clin Chem Lab Med 46:212–214

    Article  CAS  PubMed  Google Scholar 

  • Cianciolo G, La Manna G, Donati G et al (2010) Coronary calcifications in end-stage renal disease patients: a new link between osteoprotegerin, diabetes and body mass index? Blood Purif 29:13–22

    Article  CAS  PubMed  Google Scholar 

  • Evrad S, Delanaye P, Kamel S et al (2015) Vascular calcification: from pathophysiology to biomarkers. Clin Chim Acta 438:401–414

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Goustin AS, Abou-Samra AB (2011) The “thrifty” gene encoding AHSG/Fetuin-A meets the insulin receptor: insights into the mechanism of insulin resistance. Cell Signal 23:980–990

    Article  CAS  PubMed  Google Scholar 

  • Heiss A, Eckert T, Aretz A et al (2008) Hierarchical role of Fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles. J Biol Chem 283:14815–14825

    Article  CAS  PubMed  Google Scholar 

  • Herrmann M, Kinkeldey A, Jahnen-Dechent W (2012) Fetuin-A function in systemic mineral metabolism. Trends Cardiovasc Med 22(8):197–201. doi:10.1016/j.tcm.2012.07.020

    Article  CAS  PubMed  Google Scholar 

  • Ix JH, Barrett-Connor E, Wassel CL et al (2011) The association of Fetuin-A with subclinical cardiovascular disease in community-dwelling persons. The Rancho Bernardo Study. J Am Coll Cardiol 58:2372–2379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ix JH, Katz R, de Boer IH et al (2012) Fetuin-A is inversely associated with coronary artery calcification in community-living persons: the multi-ethnic study of atherosclerosis. Clin Chem 58:887–895

    Article  CAS  PubMed  Google Scholar 

  • Jensen M, Bartz T, Djoussè L et al (2013) Genetically elevated Fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes. The cardiovascular health study. Diabetes Care 36:3121–3127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkpantur A, Altun B, Hazirolan T et al (2009) Association among serum Fetuin-A level, coronary artery calcification, and bone mineral densitometry in maintenance hemodialysis patients. Artif Organs 33:844–854

    Article  CAS  PubMed  Google Scholar 

  • Lars R, Standl E, Bartnik M et al (2007) Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: the Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology [ESC] and of the European Association for the Study of Diabetes [EASD]. Eur Heart J 28:88–136

    Google Scholar 

  • Liabeuf S, Desjardins L, Diouf M et al (2015) The addition of vascular calcification scores to traditional risk factors improves cardiovascular risk assessment in patients with chronic kidney disease. PLoS One 10(7):e0131707

    Article  PubMed  PubMed Central  Google Scholar 

  • Mancia G, De Backer G, Dominiczak A et al (2007) Guidelines for the Management of Arterial Hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension [ESH] and of the European Society of Cardiology [ESC]. J Hypertens 25:1105–1187

    Article  CAS  PubMed  Google Scholar 

  • Matsui I, Hamano T, Mikami S, Fujii N, Takabatake Y, Nagasawa Y, Kawada N, Ito T, Rakugi H, Imai E, Isaka Y (2009) Fully phosphorylated Fetuin-A forms a mineral complex in the serum of rats with adenine-induced renal failure. Kidney Int 75(9):915–928. doi:10.1038/ki.2008.700

    Article  CAS  PubMed  Google Scholar 

  • Nasir K, Rubin J, Blaha MJ et al (2012) Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circ Cardiovasc Imaging 5:467–473

    Article  PubMed  Google Scholar 

  • Osawa M, Tian W, Horiuchi H, Kaneko M, Umetsu K (2005) Association of α2-HS glycoprotein [AHSG, fetuin-A] polymorphism with AHSG and phosphate serum levels. Hum Genet 116:146–151

    Article  CAS  PubMed  Google Scholar 

  • Pertosa G, Simone S, Ciccone M et al (2009) Serum Fetuin-A in hemodialysis: a link between derangement of calcium-phosphorous homeostasis and progression of atherosclerosis? Am J Kidney Dis 53:467–474

    Article  CAS  PubMed  Google Scholar 

  • Reynolds JL, Skepper JN, McNair R et al (2005) Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 16:2920–2930

    Article  CAS  PubMed  Google Scholar 

  • Roos M, Lutz J, Salmhofer H et al (2008) Relation between plasma fibroblast growth factor-23, serum Fetuin-A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function. Clin Endocrinol 68:660–665

    Article  CAS  Google Scholar 

  • Schlieper G, Brandenburg V, Djuric Z et al (2009) Risk factors for cardiovascular calcifications in non-diabetic Caucasian haemodialysis patients. Kidney Blood Press Res 32:161–168

    Article  PubMed  Google Scholar 

  • Scott M, Grundy MD et al (2002) National Cholesterol Education Panel. Third report of the National Cholesterol Education Program [NCEP] expert panel on detection, evaluation, and treatment of high blood cholesterol in adults [adult treatment panel III] final report. Circulation 106:3413–3421

    Article  Google Scholar 

  • Shroff RC, Shah V, Hiorns MP et al (2008) The circulating calcification inhibitors, Fetuin-A and osteoprotegerin, but not matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis. Nephrol Dial Transplant 23:3263–3271

    Article  CAS  PubMed  Google Scholar 

  • Stenvinkel P, Wang K, Qureshi AR, Axelsson J, Pecoits-Filho R, Gao P et al (2005) Lowfetuin-A levels are associated with cardiovascular death: impact of variation in the gene encoding fetuin. Kidney Int 67:2383–2392

    Article  CAS  PubMed  Google Scholar 

  • Trepanowski JF, Mey J, Varady KA (2015) Fetuin-A: a novel link between obesity and related complications. Int J Obes [Lond] 39:734–741

    Article  CAS  Google Scholar 

  • Wang M, Gan LY, Li SJ, Hong N, Zhang M (2009) Vascular calcification in maintenance hemodialysis patients. Blood Purif 28:15–20

    Article  PubMed  Google Scholar 

  • Zheng S, de Las Fuentes L, Bierhals A et al (2009) Relation of serum Fetuin-A levels to coronary artery calcium in African-American patients on chronic hemodialysis. Am J Cardiol 103:46–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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    Authors and Affiliations

    1. Sezione Biochimica Clinica e Medicina Molecolare Clinica, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Palermo, Italy

      Chiara Bellia, Luisa Agnello, Bruna Lo Sasso, Salvatore Milano, Giulia Bivona, Concetta Scazzone, Alessia Pivetti & Marcello Ciaccio

    2. UOC Medicina di Laboratorio - CoreLab, AOUP “P. Giaccone”, Palermo, Italy

      Marcello Ciaccio

    3. Cattedra e Divisione di Cardiologia, Università degli Studi di Palermo, Palermo, Italy

      Giuseppina Novo, Chiara Palermo, Vito Bonomo & Salvatore Novo

    4. Sezione di Scienze Radiologiche, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Palermo, Italy

      Ludovico La Grutta & Massimo Midiri

    Authors
    1. Chiara Bellia
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    2. Luisa Agnello
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    3. Bruna Lo Sasso
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    4. Salvatore Milano
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    9. Chiara Palermo
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    13. Salvatore Novo
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    14. Marcello Ciaccio
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    Correspondence to Marcello Ciaccio.

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    Chiara Bellia and Luisa Agnello have contributed equally to the study.

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    Bellia, C., Agnello, L., Lo Sasso, B. et al. Fetuin-A is Associated to Serum Calcium and AHSG T256S Genotype but Not to Coronary Artery Calcification. Biochem Genet 54, 222–231 (2016). https://doi.org/10.1007/s10528-016-9714-4

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    • DOI: https://doi.org/10.1007/s10528-016-9714-4

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