title: Gene-gene interaction between APOA5 and USF1: two candidate genes for the metabolic syndrome.
abstract: 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.
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Singmann
authors.forename: Jens
authors.initials: J
authors.lastname: Baumert
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Christina
authors.initials: C
authors.lastname: Holzapfel
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
mesh_terms: 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*
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors