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Diabetes 67, 1200-1205 (2018)
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.
Impact Factor
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Times Cited
Times Cited
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7.273
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Insulin-resistance; Tyrosine Kinase; Plasma-levels; Ahsg Gene; Association; Mellitus; Metaanalysis; Inhibitor; Interact; Receptor
Sprache
Veröffentlichungsjahr
2018
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Zeitschrift
Diabetes
Quellenangaben
Band: 67,
Heft: 6,
Seiten: 1200-1205
Verlag
American Diabetes Association
Verlagsort
Alexandria, VA.
Begutachtungsstatus
Peer reviewed
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502400-002
WOS ID
WOS:000438781600018
PubMed ID
29523632
Erfassungsdatum
2018-08-03