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Kronenberg, F.* ; Kollerits, B.* ; Kiechl, S.* ; Lamina, C.* ; Kedenko, L.* ; Meisinger, C. ; Willeit, J.* ; Huth, C. ; Wietzorrek, G.* ; Altmann, M.E.* ; Thorand, B. ; Melmer, A.* ; Dähnhardt, D.* ; Santer, P.* ; Rathmann, W.* ; Paulweber, B.* ; Koenig, W.* ; Peters, A. ; Adham, I.M.* ; Dieplinger, H.*

Plasma concentrations of afamin are associated with the prevalence and development of metabolic syndrome.

Circ. Cardiovasc. Genet. 7, 822-829 (2014)

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BACKGROUND: -Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Since little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the human afamin gene and performing large-scale human epidemiological studies. METHODS AND RESULTS: -Transgenic mice overexpressing afamin revealed increased body weight and serum concentrations of lipids and glucose. We applied a random-effects meta-analysis using age- and sex-adjusted baseline and follow-up investigations in the population-based Bruneck (n=826), SAPHIR (n=1499), and KORA F4 studies (n=3060). Mean afamin concentrations were 62.5±15.3, 66.2±14.3, and 70.6±17.2 mg/L in Bruneck, SAPHIR and KORA F4, respectively. Per 10 mg/L increment in afamin measured at baseline, the number of metabolic syndrome components increased by 19% (incidence rate ratio (IRR)=1.19 (95%CI 1.16-1.21), p=5.62×10(-64)). With the same afamin increment used at baseline we observed an 8% gain in metabolic syndrome components between baseline and follow-up (IRR=1.08 (95%CI 1.06-1.10), p=8.87×10(-16)). Afamin concentrations at baseline were highly significantly related to all individual metabolic syndrome components at baseline and follow-up. This observation was most pronounced for elevated waist circumference (OR=1.79 (95%CI 1.54-2.09), p=4.15×10(-14) at baseline and OR=1.46 (95%CI 1.31-1.63), p=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (OR=1.46 (95%CI 1.40-1.52), p=1.87×10(-69), and OR=1.46 95%CI 1.24-1.71, p=5.13×10(-6), respectively). CONCLUSIONS: -This study in transgenic mice and more than 5,000 participants in epidemiological studies shows that afamin is strongly associated with the prevalence and development of metabolic syndrome and all its components.

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