The APOA5 Trp19 allele is associated with metabolic syndrome via its association with plasma triglycerides.
BACKGROUND
The goal of the present study was to assess the effect of genetic variability at the APOA5/A4/C3/A1 cluster locus on the risk of metabolic syndrome.


METHODS
The APOA5 Ser19Trp, APOA5 -12,238T>C, APOA4 Thr347Ser, APOC3 -482C>T and APOC3 3238C>G (SstI) polymorphisms were analyzed in a representative population sample of 3138 men and women from France, including 932 individuals with metabolic syndrome and 2206 without metabolic syndrome, as defined by the NCEP criteria.


RESULTS
Compared with homozygotes for the common allele, the odds ratio (OR) [95% CI] for metabolic syndrome was 1.30 [1.03-1.66] (p = 0.03) for APOA5 Trp19 carriers, 0.81 [0.69-0.95] (p = 0.01) for APOA5 -12,238C carriers and 0.84 [0.70-0.99] (p = 0.04) for APOA4 Ser347 carriers. Adjustment for plasma triglycerides, (but not for waist girth, HDL, blood pressure or glycemia - the other components of metabolic syndrome) abolished these associations and suggests that triglyceride levels explain the association with metabolic syndrome. There was no association between the APOC3 -482C>T or APOC3 3238C>G polymorphisms and metabolic syndrome. The decreased risk of metabolic syndrome observed in APOA5 -12,238C and APOA4 Ser347 carriers merely reflected the fact that the APOA5 Trp19 allele was in negative linkage disequilibrium with the common alleles of APOA5 -12,238T>C and APOA4 Thr347Ser polymorphisms.


CONCLUSIONS
The APOA5 Trp19 allele increased susceptibility to metabolic syndrome via its impact on plasma triglyceride levels.
Dallongeville
Jean
J
Institut Pasteur de Lille, INSERM, U744, Université de Lille 2, Lille, France. jean.dallongeville@pasteur-lille.fr
Cottel
Dominique
D
Wagner
Aline
A
Ducimetière
Pierre
P
Ruidavets
Jean-Bernard
JB
Arveiler
Dominique
D
Bingham
Annie
A
Ferrières
Jean
J
Amouyel
Philippe
P
Meirhaeghe
Aline
A
D000328:Adult; D000483:Alleles; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D014280:Triglycerides
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