Journal Article

DKFZ-2018-01981

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.

Kröger, 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. ; Huerta, J. M. ; Kaaks, R.DKFZ* ; Key, T. J. ; Khaw, K. T. ; Krogh, V. ; Kühn, T.DKFZ* ; Mancini, F. R. ; Mattiello, A. ; Nilsson, P. M. ; Olsen, A. ; Overvad, K. ; Palli, D. ; Quirós, J. R. ; Rolandsson, O. ; Sacerdote, C. ; Sala, N. ; Salamanca-Fernández, 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.

2018
Assoc. Alexandria, Va

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Please use a persistent id in citations: doi:10.2337/db17-1268

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.

Keyword(s): AHSG protein, human ; Biomarkers ; alpha-2-HS-Glycoprotein

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Contributing Institute(s):

1. Epidemiologie von Krebserkrankungen (C020)

Research Program(s):

1. 323 - Metabolic Dysfunction as Risk Factor (POF3-323) (POF3-323)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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