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Genomics Day 2005: Genomics Day 2005: Public Health Genomics at CDC

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Group 4: Public Health Research and Practice

The National Birth Defects Prevention Study Centralized Laboratory
Gallagher M¹, Sturchio C¹, Honein M².
(1) NCEH
(2) NCBDDD, CDC

Apolipoprotein E polymorphism (apo E) is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease (CHD). The extent to which serial patterns of change in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations varied by apo E genotype was investigated in 247 Caucasian girls aged 8, 11, and 14 years at baseline who participated in Project HeartBeat!, a mixed longitudinal study of CVD risk factor development in children. Plasma lipid concentrations were determined 3 times a year for up to 4 years from 1991 to 1995. Analyses were adjusted for physical growth (fat-free mass, FFM), body composition (BMI and percent body fat, %BF), sexual maturation (pubic hair stage, PH), and endocrine function (estradiol, EST). Mean TC values at baseline for girls with e 2/3, e 3/3, and e 3/4 genotypes were 141.7, 161.6 and 165.9 mg/dL, respectively (p<.001). Corresponding LDL-C values were 64.6, 94.8, and 98.7 mg/dL, respectively (p<.001). The results of longitudinal modeling showed that age trajectories for TC and LDL-C varied significantly by apo E genotype. Individuals with e 3/3 and e 3/4 genotypes demonstrated similar patterns of change in TC and LDL-C from ages 8 to 18, while individuals with the e 2/3 genotype exhibited significantly lower values throughout ages 8 to 18 and different patterns of change with age for both TC and LDL-C. FFM, BMI, %BF, PH, and EST each showed a significant effect on TC and LDL-C. However, the apo E effects on TC and LDL-C remained significant after these variables were adjusted for. We conclude that the apo E effects on age-related serial changes in TC and LDL-C during adolescence are strong and independent of physical growth, body composition, sexual maturation, and estradiol level in normal adolescent girls. Girls with e 3/3 or e 3/4 genotypes may be at higher risk for elevated TC and LDL-C later in life. These genotypes may be important to identify in intervention studies or in clinical practice to evaluate responsiveness to lipid-lowering therapy.