Hepatic lipase promoter C-514T polymorphism influences serial changes in HDL cholesterol levels since childhood: the Bogalusa Heart Study.
Hepatic lipase (HL) is an important determinant of high-density lipoprotein (HDL) concentrations. A common C-to-T substitution at position -514 of the promoter region of the HL gene has been shown to be associated with HL activity and HDL cholesterol (HDL-C) levels. The current study examines the influence of this polymorphism on both levels and serial changes of HDL-C from childhood to adulthood in a community-based sample of 707 white and 291 black unrelated individuals aged 4-38 years using a repeated measures analysis. The frequency of the -514T allele was lower in whites than in blacks (0.228 vs. 0.545, P<0.001). After adjusting for age and BMI, the genotype effect on longitudinal profiles of HDL-C levels was significant (P=0.003) in white males with values in the order of T/T>T/C>C/C. Although a similar trend was seen, the genotype effect was not significant in white females and blacks. Further, the slopes of the age trajectories of HDL-C were similar in three genotype groups in blacks and whites. A sex-genotype interaction effect (P=0.043) on longitudinal profiles of HDL-C levels was found in whites, but not in blacks. White males showed a stronger genotype effect (3.6 mg/dl, P=0.003) than white females (0.5 mg/dl, P=0.601). Thus, the -514T variant of the HL gene is consistently associated with higher levels of HDL-C longitudinally since childhood, but not with rate of change over time. These results suggest that the HL gene may play an important role in the regulation of HDL-C levels from childhood to adulthood, especially in white males.
Chen
Wei
W
Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, 1440 Canal Street, Suite 2140, New Orleans, LA 70112, USA.
Srinivasan
Sathanur R
SR
Boerwinkle
Eric
E
Berenson
Gerald S
GS
D000293:Adolescent; D000328:Adult; D000368:Aged; D044383:Black People; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People
D008076:Cholesterol, HDL; D008049:Lipase