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Papers In Press, published online ahead of print December 1, 2007
J. Lipid Res., doi:10.1194/jlr.M700011-JLR200

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Journal of Lipid Research, Vol. 48, 2614-2621, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

APOA5 variants and metabolic syndrome in Caucasians

Harald Grallert^*, Eva-Maria Sedlmeier^*, Cornelia Huth^*,, Melanie Kolz^*, Iris M. Heid^*,, Christa Meisinger^*, Christian Herder, Klaus Strassburger^**, Anke Gehringer, Markus Haak, Guido Giani^**, Florian Kronenberg, H-Erich Wichmann^*,, Jerzy Adamski, Bernhard Paulweber^***, Thomas Illig^1,* and Wolfgang Rathmann^**

^* Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany
Institute of Biometry and Epidemiology, University of Munich, Munich, Germany
German Diabetes Clinic, German Diabetes Center, Leibniz Institute at Heinrich-Heine-University, Düsseldorf, Germany
^** Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute at Heinrich-Heine-University, Düsseldorf, Germany
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
Institute of Experimental Genetics, Genome Analysis Center, GSF-National Research Center for Environment and Health, Neuherberg, Germany
^*** First Department of Internal Medicine, St. Johann Spital, Paracelsus Private Medical University, Salzburg, Austria

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of three tables, one figure.

Published, JLR Papers in Press, September 3, 2007.

¹ To whom correspondence should be addressed. e-mail: illig{at}gsf.de

Apolipoprotein A5 (APOA5) gene variants were reported to be associated with two components of metabolic syndrome (MetS): higher TG levels and lower HDL levels. Moreover, a recent Japanese case-control study found variant –1131T>C associated with MetS itself. Thus, our study systematically analyzed the APOA5 gene for association with lipid parameters, any other features of MetS, including waist circumference, glucose-related parameters, blood pressure, uric acid, and MetS itself in Caucasians. Ten polymorphisms were analyzed in a large fasting sample of the population-based Cooperative Health Research in the Region of Augsburg (KORA) survey S4 (n = 1,354; southern Germany) and in a second fasting sample, the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1,770; Austria). Minor alleles of variants –1131T>C, –3A>G, c.56C>G, 476G>A, and 1259T>C were significantly associated with higher TG levels in single polymorphism (P < 0.001) and haplotype (P 6.6 x 10^–6) analysis. Besides associations with lower HDL levels in SAPHIR (P 0.001), there were no significant findings with any other features of MetS. Variant c.56C>G was associated with higher risk for MetS [odds ratio (95% confidence interval) = 1.43 (1.04, 1.99), P = 0.03 for KORA and 1.48 (1.10, 1.99), P = 0.009 for SAPHIR). Our study confirms the association of the APOA5 locus with TG and HDL levels in humans. Furthermore, the data suggest a different mechanism of APOA5 impact on MetS in Caucasians, as variant c.56C>G (not analyzed in the Japanese study) and not –1131T>C, as in the Japanese subjects, was associated with MetS.

Supplementary key words apolipoprotein • polymorphism • Cooperative Health Research in the Region of Augsburg • Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk • genetics • lipids • haplotypes • Apolipoprotein A5

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