Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronaryangiography

Coronary events have a close association with a low HDL/hypertriglyceridemi a (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipopro teins are associated with a modulation of both HDL cholesterol and triglyce rides, we have tested the hypothesis that mutations in the genes encoding l ipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the form ation of coronary atherosclerosis and, thus, of coronary heart disease (CHD ). The entire coding and boundary regions of LPL and HTGL genes were analyz ed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD . In the LPL gene six different polymorphisms were identified with same fre quencies observed in the general population. In the HTGL gene, besides seve ral polymorphisms, we identified three missense mutations: Asn37His, Val73M et, and Ser267Phe. Population screening using allele specific PCR identifie d Val73Met as a polymorphism while the two others were absent from 100 cont rol individuals. One of the mutations (Ser267Phe) is known to cause HTGL de ficiency and is associated with type III hyperlipoproteinemia. Since this d yslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to specu late that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.