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, PPARγ Pro12Ala, and TNFα -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 TNFα 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 PPARγ Pro12Ala polymorphism was found; the 12Ala PPARγ allele was rare among Blacks (2%). Conclusions: The ApoB, TNFα, 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 TNFα allele may contribute to lower HDLC in males. These gene effects and gene-environment interactions may inform prevention and treatment of atherosclerosis.