RT Journal Article
T1 Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.
A1 Kröger, Janine
A1 Meidtner, Karina
A1 Stefan, Norbert
A1 Guevara, Marcela
A1 Kerrison, Nicola D
A1 Ardanaz, Eva
A1 Aune, Dagfinn
A1 Boeing, Heiner
A1 Dorronsoro, Miren
A1 Dow, Courtney
A1 Fagherazzi, Guy
A1 Franks, Paul W
A1 Freisling, Heinz
A1 Gunter, Marc J
A1 Huerta, José María
A1 Kaaks, Rudolf
A1 Key, Timothy J
A1 Khaw, Kay Tee
A1 Krogh, Vittorio
A1 Kühn, Tilman
A1 Mancini, Francesca Romana
A1 Mattiello, Amalia
A1 Nilsson, Peter M
A1 Olsen, Anja
A1 Overvad, Kim
A1 Palli, Domenico
A1 Quirós, J Ramón
A1 Rolandsson, Olov
A1 Sacerdote, Carlotta
A1 Sala, Núria
A1 Salamanca-Fernández, Elena
A1 Sluijs, Ivonne
A1 Spijkerman, Annemieke M W
A1 Tjonneland, Anne
A1 Tsilidis, Konstantinos K
A1 Tumino, Rosario
A1 van der Schouw, Yvonne T
A1 Forouhi, Nita G
A1 Sharp, Stephen J
A1 Langenberg, Claudia
A1 Riboli, Elio
A1 Schulze, Matthias B
A1 Wareham, Nicholas J
AB 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.
YR 2018
FD 2018-03-09
LK http://hdl.handle.net/10668/12223
UL http://hdl.handle.net/10668/12223
LA en
DS RISalud
RD Apr 12, 2025