A single-nucleotide polymorphism (584C/T) in the endothelial lipase gene was significantly associated with HDL cholesterol levels in humans, complementing findings in EL-knockout mice.
Observational (n=372)
Does endothelial lipase inactivation or genetic variation affect HDL cholesterol concentration and metabolism in mice and humans?
Endothelial lipase is a major genetic determinant of HDL cholesterol concentration, structure, and metabolism in both mice and humans.
High-density lipoprotein (HDL) protects against atherosclerosis. Endothelial lipase (EL) has been postulated to be involved in lipoprotein, and possibly HDL, metabolism, yet the evidence has been scarce and conflicting. We have inactivated EL in mice by gene targeting. EL(-/-) mice have elevated plasma and HDL cholesterol, and increased apolipoproteins A-I and E. NMR analysis reveals an abundance of large HDL particles. There is down-regulation of the transcripts for phospholipid transfer protein, but up-regulation of those for hepatic lipase and lipoprotein lipase. Plasma lecithin:cholesterol acyltransferase is unchanged despite an increase in hepatic mRNA; lecithin:cholesterol acyltransferase activity toward endogenous EL(-/-) substrate is, however, reduced by 50%. HDL clearance is decreased in EL(-/-) mice; both the structure of HDL and the presence of EL are factors that determine the rate of clearance. To determine EL's role in humans, we find a significant association between a single-nucleotide polymorphism 584C/T in the EL (LIPG) gene and HDL cholesterol in a well characterized population of 372 individuals. We conclude that EL is a major determinant of HDL concentration, structure, and metabolism in mice, and a major determinant of HDL concentration in humans.
Ma 외 (Mon,)는 HDL 콜레스테롤 농도에 대한 관찰 연구를 수행했습니다 (n=372). 내피 리파제(LIPG) 유전자의 584C/T 다형성이 HDL 콜레스테롤 농도와 관련되어 평가되었습니다. 내피 리파제 유전자에서의 단일 염기 다형성(584C/T)은 인간의 HDL 콜레스테롤 수치와 유의미하게 관련되어 있으며, EL-유전자 녹아웃 생쥐의 결과를 보완합니다.