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Kroeger, J.* ; Meidtner, K.* ; Stefan, N. ; Guevara, M.* ; Kerrison, N.D.* ; Ardanaz, E.* ; Aune, D.* ; Boeing, H.* ; Dorronsoro, M.* ; Dow, C.* ; Fagherazzi, G.* ; Franks, P.W.* ; Freisling, H.* ; Gunter, M.J.* ; Maria Huerta, J.* ; Kaaks, R.* ; Key, T.J.* ; Khaw, K.T.* ; Krogh, V.* ; Kuehn, T.* ; Mancini, F.R.* ; Mattiello, A.* ; Nilsson, P.M.* ; Olsen, A.* ; Overvad, K.* ; Palli, D.* ; Ramon Quiros, J.* ; Rolandsson, O.* ; Sacerdote, C.* ; Sala, N.* ; Salamanca-Fernandez, E.* ; Sluijs, I.* ; Spijkerman, A.M.W.* ; Tjonneland, A.* ; Tsilidis, K.K.* ; Tumino, R.* ; van der Schouw, Y.T.* ; Forouhi, N.G.* ; Sharp, S.J.* ; Langenberg, C.* ; Riboli, E.* ; Schulze, M.B.* ; Wareham, N.J.*

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

Diabetes 67, 1200-1205 (2018)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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. Weaimed 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 mu g/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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Publication type Article: Journal article
Document type Scientific Article
Keywords Insulin-resistance; Tyrosine Kinase; Plasma-levels; Ahsg Gene; Association; Mellitus; Metaanalysis; Inhibitor; Interact; Receptor
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 67, Issue: 6, Pages: 1200-1205 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)