APOA5 variants and metabolic syndrome in Caucasians.
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 <or= 6.6 x 10(-6)) analysis. Besides associations with lower HDL levels in SAPHIR (P <or= 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.
Grallert
Harald
H
Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany.
Sedlmeier
Eva-Maria
EM
Huth
Cornelia
C
Kolz
Melanie
M
Heid
Iris M
IM
Meisinger
Christa
C
Herder
Christian
C
Strassburger
Klaus
K
Gehringer
Anke
A
Haak
Markus
M
Giani
Guido
G
Kronenberg
Florian
F
Wichmann
H-Erich
HE
Adamski
Jerzy
J
Paulweber
Bernhard
B
Illig
Thomas
T
Rathmann
Wolfgang
W
D000368:Aged; D000483:Alleles; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D044465:White People / Q000235:genetics*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008055:Lipids