Abstract
APOE plays a well established role in lipid metabolism. Animal model evidence suggests APOE may also be associated with adiposity, but this has not been thoroughly investigated in humans. We measured adiposity (BMI, truncal fat mass, waist circumference), physical activity (PA), cardiorespiratory fitness and APOE genotype (E2, E3, E4) in 292 8-year-old children from the Tasmanian Infant Health Survey (TIHS), an Australian population-based prospective birth cohort. Our aims were to examine the association of APOE with child adiposity, and to examine the interplay between this association and other measured factors. We found that APOE was associated with child lipid profiles. APOE was also associated with child adiposity measures. The association was E4 allele-specific, with adiposity lower in the E4-containing group (BMI: Mean difference -0.90 kg/m2; 95% confidence intervals (CI) -1.51, -0.28; p = 0.004). The association of APOE4 with lower BMI differed by fitness status (difference in effect p = 0.002), and was more evident among the less fit (mean difference -1.78 kg/m2; 95% CI -2.74, -0.83; p<0.001). Additionally, associations between BMI and lipids were only apparent in those of lower fitness who did not carry APOE4. Similar overall findings were observed when truncal fat mass and waist circumference were used as alternative adiposity measures. APOE4 and cardiorespitatory fitness could interact to influence child adiposity. In studies addressing the genetic determinants of childhood obesity, the context of child fitness should also be taken into account.
Highlights
The plasma protein apolipoprotein E, encoded by the gene APOE, plays an important role in lipid metabolism
We found strong evidence that APOE genotype was associated with LDL cholesterol (LDL-C) (p,0.001), and to a lesser extent with HDL/Total cholesterol ratio (HDL/Total-C) and log-transformed triglyceride (TG) levels
We found that the magnitude of the association between APOE4 and body mass index (BMI) was not reduced when adjusted for LDL-C (Mean difference = 0.99 kg/m2; 95% confidence intervals (CI) 0.38, 1.61; p = 0.002)
Summary
The plasma protein apolipoprotein E (apoE), encoded by the gene APOE, plays an important role in lipid metabolism. There are three isoforms; e2, e3 and e4, encoded by three alleles, E2, E3, and E4. The isoforms differ in their binding affinities for lipids and lipoprotein receptors [2]. There is a well-established relationship between serum LDL cholesterol (LDL-C) and genotypes of APOE in adults and in children. The relationship is approximately linear, with E2 associated with the lowest, and E4 associated with the highest, LDL-C, as demonstrated by Bennet and colleagues by metaanalysis [2]. Equivalent relationships between APOE genotype and LDL-C have been repeatedly demonstrated [3,4,5,6,7]
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