title: Impact of psychological stress on the associations between apolipoprotein E variants and metabolic traits: findings in an American sample of caregivers and controls.
abstract: OBJECTIVE
  To examine the association between apolipoprotein E (APOE) gene variants and waist circumference, fasting plasma glucose, serum insulin, serum high-density lipoprotein cholesterol, and serum triglycerides, all metabolic traits known as cardiovascular disease (CVD) endophenotypes, in a population of stressed individuals and controls. Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk. Current evidence supports the hypothesis that gene-environment interactions modulate serum lipid concentrations.
  
  
  METHODS
  The association between rs769450, rs405509, rs439401, and metabolic traits were analyzed in a U.S. sample of 126 white caregivers of a relative with Alzheimer';s disease or other major dementia and 122 white controls. The associations were analyzed, using multivariate analysis of variance adjusted for age, sex, and medications.
  
  
  RESULTS
  Significant multivariate interactions were found, using both additive (p = .009) and dominant (p = .047) models between rs439401 (C/T) and caregiver stress in relation to a profile of metabolic variables. Univariate analyses found the TT genotype to be associated with more adverse levels of waist circumference (interaction, p = .026), triglycerides (interaction, p = .001) and high-density lipoprotein cholesterol (interaction, p = .001) among caregivers but with a more favorable profile of these endophenotypes among controls. There were no significant associations or interactions involving the other two single nucleotide polymorphisms.
  
  
  CONCLUSIONS
  The APOE rs439401 TT genotype is associated with an adverse metabolic profile among chronically stressed individuals compared with individuals not similarly stressed in whom a more favorable profile is expressed. Confirmation of these results in further research would indicate that the TT genotype can be used to identify persons at high risk for CVD when subjected to chronic stress.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27705, USA.
authors.forename: Sofia I Iqbal
authors.initials: SI
authors.lastname: Kring
authors.forename: Beverly H
authors.initials: BH
authors.lastname: Brummett
authors.forename: John
authors.initials: J
authors.lastname: Barefoot
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Boyle
authors.forename: Ilene C
authors.initials: IC
authors.lastname: Siegler
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Redford B
authors.initials: RB
authors.lastname: Williams
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D017028:Caregivers / Q000523:psychology* / Q000706:statistics & numerical data; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013315:Stress, Psychological / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D055105:Waist Circumference / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol
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