title: Associations between APOE variants and metabolic traits and the impact of psychological stress.
abstract: OBJECTIVE
  In a previous study, we observed that associations between APOE rs439401 and metabolic traits were moderated by chronic stress. Thus, in a population of stressed and non-stressed Danish men, we examined whether associations between APOE rs439401 and a panel of metabolic quantitative traits, all metabolic traits which may lead to T2D and CVD were moderated by psychological stress.
  
  
  METHODS
  Obese young men (n = 475, BMI ≥ 31.0 kg/m(2)) and a randomly selected control group (n = 709) identified from a population of 141,800 men were re-examined in two surveys (S-46: mean age 46, S-49: mean age 49 years) where anthropometric and biochemical measures were available. Psychological stress factors were assessed by a self-administered 7-item questionnaire. Each item had the possible response categories "yes" and "no" and assessed familial problems and conflicts. Summing positive responses constituted a stress item score, which was then dichotomized into stressed and non-stressed. Logistic regression analysis, applying a recessive genetic model, was used to assess odds ratios (OR) of the associations between APOE rs439401 genotypes and adverse levels of metabolic traits.
  
  
  RESULTS
  The APOE rs439401 TT-genotype associated positively with BMI (OR = 1.09 [1.01; 1.17]), waist circumference (OR = 1.09 [1.02; 1.17]) in stressed men at S-46. Positive associations were observed for fasting plasma glucose (OR = 1.42 [1.07; 1.87]), serum triglycerides (OR = 1.41 [1.05; 1.91]) and with fasting plasma insulin (OR = 1.48 [1.05; 2.08]) in stressed men at S-49. Rs439401 TT-genotype also associated positively with surrogate measures of insulin resistance (HOMA-IR; OR = 1.21 [1.03; 1.41]) and inversely with insulin sensitivity (Stumvoll index; OR = 0.90 [0.82; 0.99], BIGTT-S(I); OR = 0.60 [0.43; 0.85]) in stressed men. No significant associations were observed in non-stressed men, albeit the estimates showed similar but weaker trends as in stressed men.
  
  
  CONCLUSIONS
  The present results suggest that the APOE rs439401 TT-genotype is associated with an adverse metabolic profile in a population of psychologically stressed Danish men.
authors.affiliation: Institute of Preventive Medicine, Copenhagen, Denmark. si@ipm.regionh.dk
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Iqbal Kring
authors.forename: John
authors.initials: J
authors.lastname: Barefoot
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Brummett
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Boyle
authors.forename: Ilene C
authors.initials: IC
authors.lastname: Siegler
authors.forename: Søren
authors.initials: S
authors.lastname: Toubro
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D001786:Blood Glucose; D001837:Body Weights and Measures; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008660:Metabolism / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013315:Stress, Psychological / Q000453:epidemiology / Q000235:genetics*; D011795:Surveys and Questionnaires; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D014280:Triglycerides