Association between hepatic lipase -514 C/T promoter polymorphism and myocardial infarction is modified by history of hypercholesterolemia and waist circumference
artículo original
Fecha
2009Autor
Baylin, Ana
Ruiz Narváez, Edward A.
Jensen, Majken K.
Rimm, Eric B.
Campos Núñez, Hannia
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Background and aims: To examine whether the association between the 514 C/T polymorphism of the hepatic lipase gene and myocardial infarction (MI) is modified by history of hypercholesterolemia and increased waist circumference. Hepatic Lipase (HL) is a major determinant of HDL cholesterol, an established independent predictor of coronary heart disease (CHD) [1]. However, the role of HL in atherosclerosis remains uncertain. Overexpression of HL in transgenic and knockout animal models has resulted in both antiatherogenic and pro-atherogenic effects [2]. Although low HL activity in humans has been identified as a risk factor for CHD [3] the net effect of HL on CHD is hard to establish given its role in lipoprotein metabolism as both a lipolytic enzyme and as a ligand that facilitates uptake of lipoproteins [4]. Four linked polymorphisms (250 G to A, 514 C to T, 710 T to C, 763 A to G) have been identified in the promoter region of the HL gene [5]. These four poly- morphisms are in complete linkage disequilibrium and together define a common HL allele designed as 514 T allele. The T allele at position 514 of the HL gene is consistently associated with lower HL activity, higher HDL cholesterol, particularly HDL2 cholesterol, higher remnant-like particles, and triglyceride content and size of HDL and LDL particles [6]. Nevertheless, evidence of the effect of the 514 T allele on CHD is inconsistent. Some studies have shown no association [7-14], while others have shown an increased risk of CHD for carriers of the 514 T allele [15-19]. Surprisingly, the 514 T allele has not been inversely associated with CHD.