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- Title
Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.
- Authors
Kröger, Janine; Meidtner, 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.; María Huerta, José; Kaaks, Rudolf; Key, Timothy J.; Kay Tee Khaw; Krogh, Vittorio; Kühn, Tilman
- 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.
- Publication
Diabetes, 2018, Vol 67, Issue 6, p1200
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db17-1268