Apo E Effects on Blood Cholesterol Are Independent of Growth and Maturation in Adolescent Girls: Project HeartBeat!
Apolipoprotein E polymorphism (apo E) is a genetic determinant of lipid and lipoprotein levels and subsequent risk for CHD. We have previously demonstrated that girls with ε3/3 or ε3/4 genotypes had both higher total (TC) and LDL-cholesterol (LDL-C) throughout ages 8 to 18 compared with those with the ε2/3 genotype. The current analysis further explored potential confounding or interaction effects of physical growth, body composition, sexual maturation, and endocrine function with apo E. In Project HeartBeat!, a mixed longitudinal study of CVD risk factor development in children, apo E genotyping was performed among 331 girls aged 8, 11, and 14 years at baseline. Plasma lipid concentrations, weight, height, body mass index (BMI), skinfolds, fat free mass (FFM), percent body fat (%BF), Tanner stage (pubic hair, PH), and endocrine function (estradiol, EST) were determined by standard methods 3 times a year for up to 4 years. Analyses were restricted to 247 Caucasian girls. The numbers of measurements used ranged from 1090 to 1960 according to the combination of variables in different multilevel linear models. FFM, BMI, %BF, PH, and EST each showed a significant effect on TC and LDL-C whether tested alone or included in models containing age (age, age 2 , and age 3 ), apo E (ε2/3, ε3/3, and ε3/4), and age-apo E interaction terms. Age, apo E, and age-apo E interaction terms were strong, independent determinants of TC and LDL-C. Except for a ε3/4-by-%BF interaction, all 2-way interaction effects between apo E and FFM, BMI, %BF, PH, and EST were not significant in either TC or LDL-C models (P>.05). We conclude that the apo E effects on age-related serial changes in TC and LDL-C are independent of physical growth, body composition, sexual maturation, and estradiol level in normal adolescent girls. Girls with ε3/3 or ε3/4 genotypes may be at higher risk for elevated TC and LDL-C later in life. These genotypes were found in 85% of the study population and may be important to identify in intervention studies or in clinical practice to evaluate responsiveness to lipid-lowering therapy.