Dataset Information

Associations between APOE variants and metabolic traits and the impact of psychological stress.

ABSTRACT: 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.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.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.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.

SUBMITTER: Iqbal Kring SI

PROVIDER: S-EPMC3023763 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Associations between APOE variants and metabolic traits and the impact of psychological stress.

Iqbal Kring Sofia I SI Barefoot John J Brummett Beverly H BH Boyle Stephen H SH Siegler Ilene C IC Toubro Søren S Hansen Torben T Astrup Arne A Pedersen Oluf O Williams Redford B RB Sørensen Thorkild I A TI

PloS one 20110119 1

<h4>Objective</h4>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.<h4>Methods</h4>Obese young men (n = 475, BMI ≥ 31.0 kg/m(2)) and a randomly selected control group ...[more]

PMID: 21283811

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Project description:The TOMM40-APOE variants are known for their strong, antagonistic associations with Alzheimer's disease and body weight. While a stronger role of the APOE than TOMM40 variants in Alzheimer's disease was suggested, comparative contribution of the TOMM40-APOE variants in the regulation of body weight remains elusive. We examined additive effects of rs2075650 and rs157580 TOMM40 variants and rs429358 and rs7412 APOE variants coding the ?2/?3/?4 polymorphism on body mass index (BMI) in age-aggregated and age-stratified cohort-specific and cohort-pooled analysis of 27,863 Caucasians aged 20-100 years from seven longitudinal studies. Minor alleles of rs2075650, rs429358, and rs7412 were individually associated with BMI (? = -1.29, p = 3.97 × 10-9 ; ? = -1.38, p = 2.78 × 10-10 ; and ? = 0.58, p = 3.04 × 10-2 , respectively). Conditional analysis with rs2075650 and rs429358 identified independent BMI-lowering associations for minor alleles (? = -0.63, p = 3.99 × 10-2 and ? = -0.94, p = 2.17 × 10-3 , respectively). Polygenic mega-analysis identified additive effects of the rs2075650 and rs429358 heterozygotes (? = -1.68, p = 3.00 × 10-9 ), and the strongest BMI-lowering association for the rs2075650 heterozygous and rs429358 minor allele homozygous carriers (? = -4.11, p = 2.78 × 10-3 ). Conditional analysis with four polymorphisms identified independent BMI-lowering (rs2075650, rs157580, and rs429358) and BMI-increasing (rs7412) associations of heterozygous genotypes with BMI. Age-stratified conditional analysis revealed well-powered support for a differential and independent association of the rs429358 heterozygote with BMI in younger and older individuals, ? = 0.58, 95% confidence interval (CI) = -1.18, 2.35, p = 5.18 × 10-1 for 3,068 individuals aged ?30 years and ? = -4.28, CI = -5.65, -2.92, p = 7.71 × 10-10 for 6,052 individuals aged >80 years. TOMM40 and APOE variants are independently and additively associated with BMI. The APOE ?4-coding rs429358 polymorphism is associated with BMI in older individuals but not in younger individuals.

Dataset Information

Associations between APOE variants and metabolic traits and the impact of psychological stress.

Publications

Associations between APOE variants and metabolic traits and the impact of psychological stress.

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