Florian Kronenberg1, Barbara Kollerits1, Stefan Kiechl1, Claudia Lamina1, Lyudmyla Kedenko1, Christa Meisinger1, Johann Willeit1, Cornelia Huth1, Georg Wietzorrek1, Maria E Altmann1, Barbara Thorand1, Andreas Melmer1, Doreen Dähnhardt1, Peter Santer1, Wolfgang Rathmann1, Bernhard Paulweber1, Wolfgang Koenig1, Annette Peters1, Ibrahim M Adham1, Hans Dieplinger2. 1. From the Division of Genetic Epidemiology (F.K., B.K., C.L., D.D., H.D.), Division of Molecular and Cellular Pharmacology, Department of Medical Genetics, Molecular, and Clinical Pharmacology (G.W.), Department of Neurology (S.K., J.W.), Department of Internal Medicine I (A.M.), Innsbruck Medical University, Innsbruck, Austria; First Department of Internal Medicine, Paracelsus Private Medical University, Salzburg, Austria (L.K., B.P.); Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Oberschleißheim, Germany (C.M., C.H., B.T., A.P.); German Center for Diabetes Research (DZD), Neuherberg, Germany (C.M., C.H., B.T., A.P.); Institute of Human Genetics, University of Göttingen, Göttingen, Germany (M.E.A. I.M.A.); Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy (P.S.); Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine, University Düsseldorf, Düsseldorf, Germany (W.R.); Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany (W.K.); and Vitateq Biotechnology GmbH, Innsbruck, Austria (H.D.). 2. From the Division of Genetic Epidemiology (F.K., B.K., C.L., D.D., H.D.), Division of Molecular and Cellular Pharmacology, Department of Medical Genetics, Molecular, and Clinical Pharmacology (G.W.), Department of Neurology (S.K., J.W.), Department of Internal Medicine I (A.M.), Innsbruck Medical University, Innsbruck, Austria; First Department of Internal Medicine, Paracelsus Private Medical University, Salzburg, Austria (L.K., B.P.); Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Oberschleißheim, Germany (C.M., C.H., B.T., A.P.); German Center for Diabetes Research (DZD), Neuherberg, Germany (C.M., C.H., B.T., A.P.); Institute of Human Genetics, University of Göttingen, Göttingen, Germany (M.E.A. I.M.A.); Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy (P.S.); Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine, University Düsseldorf, Düsseldorf, Germany (W.R.); Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Ulm, Germany (W.K.); and Vitateq Biotechnology GmbH, Innsbruck, Austria (H.D.). hans.dieplinger@i-med.ac.at.
Abstract
BACKGROUND: Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Because 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), Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR; n=1499), and KOoperative Gesundheitsforschung in der Region Augsburg (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=1.19; 95% confidence interval [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 (incidence rate ratio=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 at follow-up. This observation was most pronounced for elevated waist circumference (odds ratio, 1.79; 95% CI, 1.54-2.09; P=4.15×10(-14) at baseline and odds ratio, 1.46; 95% CI, 1.31-1.63; P=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (odds ratio, 1.46; 95% CI, 1.40-1.52; P=1.87×10(-69) and odds ratio, 1.46; 95% CI, 1.24-1.71; P=5.13×10(-6), respectively). CONCLUSIONS: This study in transgenic mice and >5000 participants in epidemiological studies shows that afamin is strongly associated with the prevalence and development of metabolic syndrome and all its components.
BACKGROUND:Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Because little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the humanafamin 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), Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR; n=1499), and KOoperative Gesundheitsforschung in der Region Augsburg (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=1.19; 95% confidence interval [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 (incidence rate ratio=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 at follow-up. This observation was most pronounced for elevated waist circumference (odds ratio, 1.79; 95% CI, 1.54-2.09; P=4.15×10(-14) at baseline and odds ratio, 1.46; 95% CI, 1.31-1.63; P=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (odds ratio, 1.46; 95% CI, 1.40-1.52; P=1.87×10(-69) and odds ratio, 1.46; 95% CI, 1.24-1.71; P=5.13×10(-6), respectively). CONCLUSIONS: This study in transgenic mice and >5000 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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