title: Apolipoprotein E4 association with metabolic syndrome depends on body fatness.
abstract: OBJECTIVE
  The human Apolipoprotein E (APOE) gene is polymorphic. The APOE*4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (MetS) as it may affect all MetS components. We hypothesize that the common APOE4 polymorphism differentially regulates MetS risk and that this association might be modulated by body fatness.
  
  
  RESULTS
  We used body mass index (BMI) as surrogate of fatness and cross-sectionally studied the prevalence of MetS in 4408 middle-aged men of the Aragon Workers Health Study (AWHS). Our analysis revealed i) a gene dose-dependent association between APOE*4 allele and increased risk for MetS, ii) this association primarily derived from the overweight subjects. For these individuals, the MetS risk was higher in APOE*4 carriers than in non-carriers (Odds Ratio = 1.31; 95% CI, 1.03-1.67). Additionally, we examined 3908 healthy young individuals from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, followed-up for 25 years. Compared with APOE*4 non-carriers, APOE*4 presence significantly increased the risk of developing MetS (Hazard Ratio, 1.12; 95% CI, 1.00-1.26). Again, an interplay between APOE*4 and the longitudinal development of fatness towards the onset of MetS occurred throughout the study. For individuals with BMI gain below the median, the cumulative onset rate of MetS was significantly higher in APOE*4 carriers than in the non-carriers (HR, 1.29; 95% CI, 1.07-1.55).
  
  
  CONCLUSIONS
  Carrying APOE*4 alleles increases MetS in a dose-dependent manner, characterizing individual's APOE genotype might help identify at-risk subjects for preventive intervention.
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Torres-Perez
authors.affiliation: Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain; Unidad de Prevención Cardiovascular, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ledesma
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Garcia-Sobreviela
authors.affiliation: Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain; Unidad de Prevención Cardiovascular, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Leon-Latre
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain. Electronic address: jmarbones.iacs@aragon.es.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Arbones-Mainar
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D015992:Body Mass Index; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D050177:Overweight / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; D004247:DNA
keywords: APOE4; AWHS; CARDIA; Metabolic syndrome