Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.
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Authors
Kröger, JanineMeidtner, Karina
Stefan, Norbert
Guevara, Marcela
Kerrison, Nicola D
Ardanaz, Eva
Aune, Dagfinn
Boeing, Heiner
Dorronsoro, Miren
Dow, Courtney
Fagherazzi, Guy
Franks, Paul W
Freisling, Heinz
Gunter, Marc J
Huerta, José María
Kaaks, Rudolf
Key, Timothy J
Khaw, Kay Tee
Krogh, Vittorio
Kühn, Tilman
Mancini, Francesca Romana
Mattiello, Amalia
Nilsson, Peter M
Olsen, Anja
Overvad, Kim
Palli, Domenico
Quirós, J Ramón
Rolandsson, Olov
Sacerdote, Carlotta
Sala, Núria
Salamanca-Fernández, Elena
Sluijs, Ivonne
Spijkerman, Annemieke Mw
Tjonneland, Anne
Tsilidis, Konstantinos K
Tumino, Rosario
van der Schouw, Yvonne T
Forouhi, Nita G
Sharp, Stephen J
Langenberg, Claudia
Riboli, Elio
Schulze, Matthias B
Wareham, Nicholas J
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ArticleLanguage
en
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Show full item recordTitle
Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.Published in
Diabetes 2018; 67(6):1200-5Publiekssamenvatting
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 SNPs located in the fetuin-A-encodingAHSGgene. We used data from eight European countries of the prospective 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 cases. A genetic score of theAHSGSNPs 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 (HR 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 cases) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistical evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study doesn't support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.DOI
10.2337/db17-1268PMID
29523632ae974a485f413a2113503eed53cd6c53
10.2337/db17-1268
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