title: The apolipoprotein E polymorphism rs7412 associates with body fatness independently of plasma lipids in middle aged men.
abstract: BACKGROUND
  The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.
  
  
  METHODS
  We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.
  
  
  RESULTS
  The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01-1.59).
  
  
  CONCLUSIONS
  This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.
authors.affiliation: Departamento de Anatomía, Embriología y Genética, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Tejedor
authors.affiliation: Adipocyte and Fat Biology Laboratory (AdipoFat), Unidad de Investigación Traslacional, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Garcia-Sobreviela
authors.affiliation: 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, Instituto Aragonés de Ciencias de la Salud (IACS), Hospital Universitario Miguel Servet, Zaragoza, Spain; CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Arbones-Mainar
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D005091:Exons; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D014280:Triglycerides