Gene-gene interaction between APOA5 and USF1: two candidate genes for the metabolic syndrome.
OBJECTIVE
The metabolic syndrome, a major cluster of risk factors for cardiovascular diseases, shows increasing prevalence worldwide. Several studies have established associations of both apolipoprotein A5 (APOA5) gene variants and upstream stimulatory factor 1 (USF1) gene variants with blood lipid levels and metabolic syndrome. USF1 is a transcription factor for APOA5.


METHODS
We investigated a possible interaction between these two genes on the risk for the metabolic syndrome, using data from the German population-based KORA survey 4 (1,622 men and women aged 55-74 years). Seven APOA5 single nucleotide polymorphisms (SNPs) were analyzed in combination with six USF1 SNPs, applying logistic regression in an additive model adjusting for age and sex and the definition for metabolic syndrome from the National Cholesterol Education Program's Adult Treatment Panel III (NCEP (AIII)) including medication.


RESULTS
The overall prevalence for metabolic syndrome was 41%. Two SNP combinations showed a nominal gene-gene interaction (p values 0.024 and 0.047). The effect of one SNP was modified by the other SNP, with a lower risk for the metabolic syndrome with odds ratios (ORs) between 0.33 (95% CI = 0.13-0.83) and 0.40 (95% CI = 0.15-1.12) when the other SNP was homozygous for the minor allele. Nevertheless, none of the associations remained significant after correction for multiple testing.


CONCLUSIONS
Thus, there is an indication of an interaction between APOA5 and USF1 on the risk for metabolic syndrome.
Singmann
Paula
P
Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Baumert
Jens
J
Herder
Christian
C
Meisinger
Christa
C
Holzapfel
Christina
C
Klopp
Norman
N
Wichmann
H-Erich
HE
Klingenspor
Martin
M
Rathmann
Wolfgang
W
Illig
Thomas
T
Grallert
Harald
H
D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005858:Germany / Q000453:epidemiology; D006720:Homozygote; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D013489:Suppression, Genetic; D051720:Upstream Stimulatory Factors / Q000235:genetics*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors