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

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

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 r...

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Main Authors: Kröger, J, Meidtner, K, Stefan, N, Guevara, M, Kerrison, ND, Ardanaz, E, Aune, D, Boeing, H, Dorronsoro, M, Dow, C, Fagherazzi, G, Franks, PW, Freisling, H, Gunter, MJ, Huerta, JM, Kaaks, R, Key, TJ, Khaw, KT, Krogh, V, Kühn, T, Mancini, FR, Mattiello, A, Nilsson, PM, Olsen, A, Overvad, K, Palli, D, Quirós, JR, Rolandsson, O, Sacerdote, C, Sala, N, Salamanca-Fernández, E, Sluijs, I, Spijkerman, AMW, Tjonneland, A, Tsilidis, KK, Tumino, R, Van Der Schouw, YT, Forouhi, NG, Sharp, SJ, Langenberg, C, Riboli, E, Schulze, MB, Wareham, NJ
格式: Journal article
語言:English
出版: American Diabetes Association 2018
實物特徵
總結: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.

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