Association between _APOE_ genotype with body composition and cardiovascular disease risk markers is modulated by BMI in healthy adults: Findings from the BODYCON study
E. Ozen, R. Mihaylova, N. J. Lord, J. A. Lovegrove and K. G. Jackson
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences and Institute for Cardiovascular and Metabolic Research and Institute for Food, Nutrition and Health,_ _University of Reading, Whiteknights, Reading, RG6 6DZ, UK
The relationship between _APOLIPOPROTEIN (APO)E_ genotype and cardiovascular disease (CVD) risk is extensively studied due to its effect on the plasma lipid profile(1). However, studies investigating the associations between _APOE_ genotype with CVD risk markers have generated inconsistent results, with a small number of human studies suggesting that BMI might play an important role in this relationship(2, 3).Therefore, we assessed the association between _APOE_ genotype with body composition and CVD risk markers, with further examination of the role of BMI on this association.
BODYCON (impact of physiological and lifestyle factors on body composition) was a cross-sectional observational study in which 360 healthy men and women aged 18-70 y with a BMI of 18.5-39.9 kg/m2 underwent a measure of body composition by dual energy x-ray absorptiometry, assessment of physical activity level using a tri-axial accelerometer and habitual dietary intake using a 4-day weighed food diary. Circulating lipid CVD risk markers were measured in a fasting blood sample and participants were genotyped retrospectively for _APOE_ (rs429358 and rs7412). A general linear model was used to determine the impact of genotype on body composition measures and CVD risk markers, and interaction between _APOE_ and BMI on these outcome measures.
In the study cohort, n=46 participants were _APOE2/E3_, n=228 the wild type _APOE3/E3_group and n=81 _E4_ carriers (_APOE3/E4_ and _APOE4/E4_)._ _The_APOE2/E3_ group had on average 9%-18% lower fasting total, low-density lipoprotein and non-high density lipoprotein cholesterol concentrations compared to the _APOE4_ carrier and _APOE3/E3_ groups_ _(p≤0.01). Significant _APOE_ x BMI interactions were observed for body weight and android fat mass (p≤0.01). When the group were stratified into normal-weight and overweight/obese BMI subgroups, lean body mass was 6.4% lower in the _APOE3/E3_ group (45.2(SE 0.5) kg) compared to the _APOE4_ carriers (48.1(SE 0.9) kg)_ _in the normal BMI subgroup (p≤0.02), while in the overweight/obese BMI subgroup, the android:gynoid fat ratio was 7.6% lower in the _APOE4_ carriers (1.10(SE 0.03) compared to the _APOE3/E3_ group (1.19(SE 0.02) (p=0.04). Differences in fasting lipid concentrations between the _APOE2/E3_ and other genotype groups was only found within the normal weight (p≤0.04) but not overweight/obese BMI subgroup. Moreover, the _APOE2/E3_ participants within the normal-weight BMI subgroup had a lower dietary fibre and trans-fat intake compared to the _APOE4_ carriers and lower carbohydrate intake compared to the _APOE3/E3_group while there were no differences between genotypes in the overweight/obese BMI subgroup. Physical activity levels were similar between genotype groups within each BMI subgroup.
Our findings confirm previous studies suggesting that the impact of** **_APOE_genotype on lipid CVD risk markers is modulated by BMI but indicate that diet may also play a role in this relationship. Further research is needed to draw a firm conclusion on the underlying mechanisms.
1. Bennet AM, Di Angelantonio E, Ye Z et al. (2007) _Jama_ 298, 1300-1311.
2. Kofler BM, Miles EA, Curtis P et al. (2012) _Atherosclerosis_ 221,467-470.
3. Minihane AM, Khan S, Leigh-Firbank EC et al. (2000) _Arterioscler Thromb Vasc Biol_ 20,1990-1997.

Association between APOE genotype with body composition and cardiovascular disease risk markers is modulated by BMI in healthy adults: findings from the BODYCON study

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