APOA5 variants and metabolic syndrome in Caucasianss

• Published in: Journal of lipid research 2007-12, Vol.48 (12), p.2614-2621
• Main Authors: Grallert, Harald, Sedlmeier, Eva-Maria, Huth, Cornelia, Kolz, Melanie, Heid, Iris M., Meisinger, Christa, Herder, Christian, Strassburger, Klaus, Gehringer, Anke, Haak, Markus, Giani, Guido, Kronenberg, Florian, Wichmann, H-Erich, Adamski, Jerzy, Paulweber, Bernhard, Illig, Thomas, Rathmann, Wolfgang
• Format: Article
• Language: English
• Subjects: apolipoprotein; Apolipoprotein A5; Cooperative Health Research in the Region of Augsburg; genetics; haplotypes; lipids; polymorphism; Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M700011-JLR200

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 × 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.