Background/Aims: Fetuin-A is a negative acute-phase reactant and extraosseous calcification inhibitor. Decreased serum concentration of fetuin-A is independently related to all-cause and cardiovascular mortality in dialysis patients. Our aim is to investigate the association between the genetic polymorphism of α2-Heremans-Schmid-glycoprotein (AHSG) encoding fetuin-A and its serum concentration, vascular calcification, and aortic stiffness in peritoneal dialysis (PD) patients. Method: A total of six single nucleotide polymorphisms (SNPs) in the AHSG gene were genotyped and evaluated for association with serum fetuin-A level, quantitative measures of vascular calcification and aortic stiffness represented by heart-to-femoral pulse wave velocity (hfPWV). Results: Five SNPs in the AHSG gene were nominally associated with the serum fetuin-A level in our PD patients. In haplotype analyses, there were haplotypes positively (H1; AGCA, H2; CC) and inversely (H1; TTCG, H2; TT) related with the serum fetuin-A level. The serum fetuin-A level inversely and independently correlated with hfPWV. Moreover, the serum fetuin-A concentration was a determinant for the simple vascular calcification score (SVCS), which subsequently was associated with hfPWV. Conclusions: Our study showed an association between AHSG polymorphism and its serum concentration, and also revealed an association of the serum fetuin-A level with SVCS and aortic stiffness in PD patients.

1.
Foley R, Parfrey P, Sarnak M: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S112–S119.
2.
Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W: The serum protein α2-heremans-schmid glycoprotein/fetuin-a is a systemically acting inhibitor of ectopic calcification. J Clin Invest 2003;112:357–366.
3.
Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Böhm 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.
4.
Hermans MMH, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Boeschoten EW, Leunissen KML, Krediet RT, Dekker FW: Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int 2007;72:202–207.
5.
London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H: Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003;18:1731–1740.
6.
Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM: Impact of aortic stiffness on survival in end-stage renal disease. Circulation 1999;99:2434–2439.
7.
Hermans MMH, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Gladziwa U, Rensma PL, Bartelet K, Konings CJAM, Hoeks APG, Floege J, Leunissen KML: Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant 2006;21:1293–1299.
8.
Stenvinkel P, Wang K, Qureshi AR, Axelsson J, Pecoits-Filho R, Gao P, Barany P, Lindholm B, Jogestrand T, Heimburger O, Holmes C, Schalling M, Nordfors L: Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int 2005;67:2383–2392.
9.
Inoue M, Takata H, Ikeda Y, Suehiro T, Inada S, Osaki F, Arii K, Kumon Y, Hashimoto K: A promoter polymorphism of the alpha2-HS glycoprotein gene is associated with its transcriptional activity. Diabetes Res Clin Pract 2008;79:164–170.
10.
Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263–265.
11.
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.
12.
Lehtinen AB, Burdon KP, Lewis JP, Langefeld CD, Ziegler JT, Rich SS, Register TC, Carr JJ, Freedman BI, Bowden DW: Association of alpha2-Heremans-Schmid glycoprotein polymorphisms with subclinical atherosclerosis. J Clin Endocrinol Metab 2007;92:345–352.
13.
Adragao T, Pires A, Lucas C, Birne R, Magalhaes L, Goncalves M, Negrao AP: A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant 2004;19:1480–1488.
14.
Munakata M, Ito N, Nunokawa T, Yoshinaga K: Utility of automated brachial ankle pulse wave velocity measurements in hypertensive patients. Am J Hypertens 2003;16:653–657.
15.
Kimoto E, Shoji T, Shinohara K, Inaba M, Okuno Y, Miki T, Koyama H, Emoto M, Nishizawa Y: Preferential stiffening of central over peripheral arteries in type 2 diabetes. Diabetes 2003;52:448–452.
16.
Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, Koji Y, Hori S, Yamamoto Y: Validity, reproducibility, and clinical significance of noninvasive brachial- ankle pulse wave velocity measurement. Hypertens Res 2002;25:359–364.
17.
Osawa M, Umetsu K, Sato M, Ohki T, Yukawa N, Suzuki T, Takeichi S: Structure of the gene encoding human alpha 2-HS glycoprotein (AHSG). Gene 1997;196:121–125.
18.
Lavebratt C, Wahlqvist S, Nordfors L, Hoffstedt J, Arner P: AHSG gene variant is associated with leanness among Swedish men. Hum Genet 2005;117:54–60.
19.
Moe SM, Reslerova M, Ketteler M, O’Neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX: Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int 2005;67:2295–2304.
20.
KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009:S1–S130.
21.
Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PWF: New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 1997;132:245–250.
22.
Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, Lui SF, Li PKT, Sanderson JE: 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.
23.
Pecoits-Filho R, Heimburger O, Barany P, Suliman M, Fehrman-Ekholm I, Lindholm B, Stenvinkel P: Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003;41:1212–1218.
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