Genetic and environmental determinants of lipid profile in black and white youth: a study of four candidate genes.

OBJECTIVE

To identify genotypes and gene-environment interactions, which may explain ethnic differences on lipid profile in Black and White youth.

DESIGN, SETTING, PARTICIPANTS: Healthy adolescents and young adults (N=413, 18.6 +/-2.8 yrs, 44% Black, 53% Male) drawn from a cardiovascular study.

MAIN OUTCOME MEASURES

Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and triglyceride (TG) concentrations were obtained from frozen plasma. The ApoB Glu4154Lys, LDL receptor (LDLR) T1773C, PPARgamma Pro12Ala, and TNFalpha -308G/A polymorphisms were genotyped. Analyses adjusted for age, sex, ethnicity, body mass index (BMI), socioeconomic status (SES), and interactions.

RESULTS

The ApoB Glu4154Lys polymorphism interacted with obesity and age to predict TC levels. As BMI increased, 4154Lys ApoB allele carriers had higher TC levels than 4154Glu homozygotes (difference=0.23 mmol/L at BMI=30 kg/m2, 0.54 at BMI=40, P<.05). Juvenile, but not adult, ApoB 4154Lys allele carriers had higher TC (0.34 mmol/L, P<.01). Male -308A TNFalpha allele carriers had lower HDLC (0.10 mmol/L, P<.01). Carriers of the T1 773 LDLR allele had higher TG (0.26 mmol/ L, P<.01). No effect of the PPARgamma Pro12Ala polymorphism was found; the 12Ala PPARgamma allele was rare among Blacks (2%).

CONCLUSIONS

The ApoB, TNFalpha, and LDLR candidate genes influenced lipid profiles in youth independent of environmental factors. The T1773 LDLR allele, which is rare among Blacks (7%), may contribute to lower TG in Blacks. The -308A TNFalpha allele may contribute to lower HDLC in males. These gene effects and gene-environment interactions may inform prevention and treatment of atherosclerosis.