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Circulating fetuin - A and risk of type 2 diabetes : A mendelian randomization analysis

Kröger, Janine; Meidtner, Karina; Stefan, Norbert; Guevara, Marcela; Kerrison, Nicola D.; Ardanaz, Eva LU ; Aune, Dagfinn; Boeing, Heiner; Dorronsoro, Miren and Dow, Courtney, et al. (2018) In Diabetes 67(6). p.1200-1205
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... (More)

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 mg/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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published
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Diabetes
volume
67
issue
6
pages
6 pages
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85047763125
ISSN
0012-1797
DOI
10.2337/db17-1268
language
English
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yes
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67a8040a-370e-4783-abac-00be52504d9f
date added to LUP
2018-06-12 13:55:29
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2018-06-13 03:00:02
@article{67a8040a-370e-4783-abac-00be52504d9f,
  abstract     = {<p>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 mg/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.</p>},
  author       = {Kröger, Janine and Meidtner, Karina and Stefan, Norbert and Guevara, Marcela and Kerrison, Nicola D. and Ardanaz, Eva and Aune, Dagfinn and Boeing, Heiner and Dorronsoro, Miren and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Freisling, Heinz and Gunter, Marc J. and Huerta, José María and Kaaks, Rudolf and Key, Timothy J. and Khaw, Kay Tee and Krogh, Vittorio and Kühn, Tilman and Mancini, Francesca Romana and Mattiello, Amalia and Nilsson, Peter M. and Olsen, Anja and Overvad, Kim and Palli, Domenico and Quirós, J. Ramón and Rolandsson, Olov and Sacerdote, Carlotta and Sala, Núria and Salamanca-Fernández, Elena and Sluijs, Ivonne and Spijkerman, Annemieke M.W. and Tjonneland, Anne and Tsilidis, Konstantinos K. and Tumino, Rosario and Van Der Schouw, Yvonne T. and Forouhi, Nita G. and Sharp, Stephen J. and Langenberg, Claudia and Riboli, Elio and Schulze, Matthias B. and Wareham, Nicholas J.},
  issn         = {0012-1797},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1200--1205},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Circulating fetuin - A and risk of type 2 diabetes : A mendelian randomization analysis},
  url          = {http://dx.doi.org/10.2337/db17-1268},
  volume       = {67},
  year         = {2018},
}