J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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A more recent version of this article appeared on December 1, 2007

Papers In Press, published online ahead of print September 3, 2007
J. Lipid Res., doi:10.1194/jlr.M700011-JLR200
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Submitted on January 8, 2007
Revised on August 23, 2007
Accepted on September 3, 2007

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, and Wolfgang Rathmann

Epidemiology, GSF - National Research Center for Environment and Health, Neuherberg, Bavaria 85764

Corresponding Author: 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 being 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 KORA survey S4 (n=1354) (Southern Germany), and in a second fasting sample, the SAPHIR study (n=1770) (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 analysis (p=6.6×10-6). 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 ratios (OR) [CI 95%] 1.43 [1.04,1.99] p=0.03 KORA; 1.48 [1.10,1.99] p=0.009 SAPHIR). Our study confirms association of the APOA5 locus with TG and HDL levels in humans. Furthermore, 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 Japanese, was associated with MetS.


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