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Observational Study
. 2018 Jun;67(6):1200-1205.
doi: 10.2337/db17-1268. Epub 2018 Mar 9.

Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis

Janine Kröger  1   2 , Karina Meidtner  1   2 , Norbert Stefan  2   3   4 , Marcela Guevara  5   6   7 , Nicola D Kerrison  8 , Eva Ardanaz  5   6   7 , Dagfinn Aune  9   10 , Heiner Boeing  11 , Miren Dorronsoro  7   12   13 , Courtney Dow  14   15   16 , Guy Fagherazzi  14   15   16 , Paul W Franks  17   18 , Heinz Freisling  19 , Marc J Gunter  19 , José María Huerta  7   20 , Rudolf Kaaks  21 , Timothy J Key  22 , Kay Tee Khaw  23 , Vittorio Krogh  24 , Tilman Kühn  25 , Francesca Romana Mancini  14   15   16 , Amalia Mattiello  26 , Peter M Nilsson  17 , Anja Olsen  27 , Kim Overvad  28   29 , Domenico Palli  30 , J Ramón Quirós  31 , Olov Rolandsson  18 , Carlotta Sacerdote  32   33 , Núria Sala  34 , Elena Salamanca-Fernández  7   35   36 , Ivonne Sluijs  37 , Annemieke M W Spijkerman  38 , Anne Tjonneland  27 , Konstantinos K Tsilidis  9   39 , Rosario Tumino  40   41 , Yvonne T van der Schouw  37 , Nita G Forouhi  8 , Stephen J Sharp  8 , Claudia Langenberg  8 , Elio Riboli  42 , Matthias B Schulze  43   2   44 , Nicholas J Wareham  8
Affiliations
Observational Study

Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis

Janine Kröger et al. Diabetes. 2018 Jun.

Abstract

Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.

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Conflict of interest statement

Duality of Interest. No conflicts of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
Construction of the EPIC-InterAct case-cohort study and the study populations used for the present analysis
See this image and copyright information in PMC

References

    1. 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. 2006;29:853–857. - PubMed
    1. Denecke B, Graber S, Schafer C, Heiss A, Woltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J. 2003;376:135–145. - PMC - PubMed
    1. Auberger P, Falquerho L, Contreres JO, Pages G, Le Cam G, Rossi B, Le Cam A. Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell. 1989;58:631–640. - PubMed
    1. Rauth G, Poschke O, Fink E, Eulitz M, Tippmer S, Kellerer M, Haring HU, Nawratil P, Haasemann M, Jahnen-Dechent W, et al. The nucleotide and partial amino acid sequences of rat fetuin. Identity with the natural tyrosine kinase inhibitor of the rat insulin receptor. European journal of biochemistry / FEBS. 1992;204:523–529. - PubMed
    1. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS, Jen KL, Charron MJ, Jahnen-Dechent W, Grunberger G. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes. 2002;51:2450–2458. - PubMed

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