Effects of apolipoprotein E genotype on blood cholesterol in adolescent girls.

Background: Few investigations have examined whether associations between the apolipoprotein E genotype (apo E) and total cholesterol or LDL-C are modified or explained by other characteristics. The objective of this study was to explore effects of behavioral characteristics, physical growth, body composition, sexual maturation, and endocrine function on age trajectories of total cholesterol and LDL-C by apo E in adolescent girls.

Methods: Participants were 247 Caucasian adolescent girls followed for 4 years. Apo E genotyping and plasma lipid concentrations were determined from fasting blood samples using standard enzymatic methods. Age; gender; fat-free mass (FFM); BMI; percent body fat (PBF); sexual maturation (pubic hair, Tanner Stages 1-5); estradiol concentration (EST); energy intake; and physical activity were collected or calculated with standard methods.

Results: In models including the proposed explanatory variables, apo E genotype remained strongly associated with total cholesterol and LDL-C. Girls with the epsilon (epsilon)3/3 and epsilon3/4 genotypes (where epsilon is the protein isoform of the apo E gene), relative to those with epsilon2/3, had total cholesterol and LDL-C values 16-23 mg/dL higher throughout adolescence. Age-apo E interaction terms remained significant. FFM, BMI, PBF, pubic-hair stage, and EST showed a significant effect on total cholesterol and LDL-C. When the combination of pubic-hair stage, EST, and one of FFM, BMI, and PBF was included in total cholesterol or LDL-C models, only EST was significant.

Conclusions: Adolescent girls with epsilon3/3 and epsilon3/4 genotypes had higher total cholesterol and LDL-C and showed different patterns of change, compared to those with epsilon2/3 genotype. These apo E effects were independent of behavioral characteristics, physical growth, body composition, sexual maturation, and endocrine function. Girls with epsilon3/3 or epsilon3/4 genotypes may be at risk for elevated total cholesterol and LDL-C later in life.