| Literature DB >> 29523632 |
Janine Kröger1,2, Karina Meidtner1,2, Norbert Stefan2,3,4, Marcela Guevara5,6,7, Nicola D Kerrison8, Eva Ardanaz5,6,7, Dagfinn Aune9,10, Heiner Boeing11, Miren Dorronsoro7,12,13, Courtney Dow14,15,16, Guy Fagherazzi14,15,16, Paul W Franks17,18, Heinz Freisling19, Marc J Gunter19, José María Huerta7,20, Rudolf Kaaks21, Timothy J Key22, Kay Tee Khaw23, Vittorio Krogh24, Tilman Kühn25, Francesca Romana Mancini14,15,16, Amalia Mattiello26, Peter M Nilsson17, Anja Olsen27, Kim Overvad28,29, Domenico Palli30, J Ramón Quirós31, Olov Rolandsson18, Carlotta Sacerdote32,33, Núria Sala34, Elena Salamanca-Fernández7,35,36, Ivonne Sluijs37, Annemieke M W Spijkerman38, Anne Tjonneland27, Konstantinos K Tsilidis9,39, Rosario Tumino40,41, Yvonne T van der Schouw37, Nita G Forouhi8, Stephen J Sharp8, Claudia Langenberg8, Elio Riboli42, Matthias B Schulze43,2,44, Nicholas J Wareham8.
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.Entities:
Mesh：
Substances：
Year: 2018 PMID： 29523632 PMCID： PMC6278908 DOI： 10.2337/db17-1268
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461