Key result
APOE rs439401 TT genotype plus chronic stress is linked to worse metabolic risk profiles.
Why the study?
Abdominal obesity, insulin resistance, elevated serum lipid concentration, and APOE polymorphisms have been associated with CVD risk, and gene-environment interactions may modulate serum lipid concentrations under stress.
Does chronic caregiver stress modulate the association between APOE gene variants and metabolic traits associated with cardiovascular disease risk?
Observational (n=248)
Does chronic caregiver stress modulate the association between APOE gene variants and metabolic traits associated with cardiovascular disease risk?
p-value: p=0.009
The APOE rs439401 TT genotype is associated with an adverse metabolic profile in chronically stressed individuals, highlighting a gene-environment interaction that may identify persons at high risk for cardiovascular disease.
No immediate clinical genotyping or intervention changes; leaves open replication of APOE-stress metabolic interactions in larger cohorts.
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. CONCLUSION: 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.
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Kring et al. (2010) conducted an observational in Caregiver stress and cardiovascular disease endophenotypes (n=248). APOE rs439401 TT genotype and caregiver stress vs. Controls without chronic caregiver stress and other APOE genotypes was evaluated on Profile of metabolic variables (waist circumference, fasting plasma glucose, serum insulin, HDL cholesterol, and triglycerides) (p=0.009). The APOE rs439401 TT genotype interacted with caregiver stress to produce an adverse metabolic profile, including worse waist circumference and triglycerides, compared to unstressed controls (p=0.009).
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