• DOI:10.1093/ndt/gfq402
• Corpus ID: 1976011

Is fetuin-A a mortality risk factor in dialysis patients or a mere risk marker? A Mendelian randomization approach.

@article{Verduijn2011IsFA,
  title={Is fetuin-A a mortality risk factor in dialysis patients or a mere risk marker? A Mendelian randomization approach.},
  author={Marion Verduijn and Robert Prein and Peter Stenvinkel and Juan Jes{\'u}s Carrero and Saskia le Cessie and Anna Witasp and Louise Nordfors and Raymond T. Krediet and Elisabeth Wilhelmina Boeschoten and Friedo W Dekker},
  journal={Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
  year={2011},
  volume={26 1},
  pages={
          239-45
        }
}

• M. Verduijn, Robert Prein, +7 authors F. Dekker
• Published 2011
• Medicine, Biology
• Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

BACKGROUND
Low levels of circulating fetuin-A are associated with increased mortality in dialysis patients. This study aimed to examine a potential causative role for fetuin-A on mortality by investigating whether a functional polymorphism in the alpha2-Heremans-Schmid glycoprotein (AHSG) gene associates with mortality, and by estimating the causative effect of fetuin-A levels on mortality using a Mendelian randomization design.

METHODS
One thousand and forty-three incident dialysis patients were genotyped for the Thr256Ser polymorphism (rs4918) and followed up for 5 years; in 549 patients, serum fetuin-A levels were measured.

RESULTS
Carriers of a serine allele displayed lower fetuin-A levels (-0.07 g/L per allele, P < 0.001). A small increased mortality risk was observed for the Thr/Ser and Ser/Ser genotype compared with the Thr/Thr genotype (HR 1.03, 95% CI 0.83-1.28 and HR 1.10, 95% CI 0.78-1.55, respectively). Using the AHSG genotype as an instrumental variable, the causative HR of fetuin-A levels on mortality was estimated as 1.01 per 0.1-g/L increase. Inflammation and diabetes partially modified the association of fetuin-A levels with outcome.

CONCLUSIONS
The Thr256Ser polymorphism was weakly associated with mortality, and no causative effect of fetuin-A levels on this outcome was observed. Other risk factors, including inflammation and diabetes, might lead to lower fetuin-A levels, and/or modify the effect of low fetuin-A on mortality in end-stage renal disease patients.