title: Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography.
abstract: Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD. In the LPL gene six different polymorphisms were identified with same frequencies observed in the general population. In the HTGL gene, besides several polymorphisms, we identified three missense mutations: Asn37His, Val73Met, and Ser267Phe. Population screening using allele specific PCR identified Val73Met as a polymorphism while the two others were absent from 100 control individuals. One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia. Since this dyslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to speculate that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype.
authors.affiliation: Department of Cardiology and Angiology, Westfälische Wilhelms-University, Albert-Schweitzer-Str. 33, D-48149, Münster, Germany. moennig@uni-muenster.de
authors.forename: G
authors.initials: G
authors.lastname: Moennig
authors.forename: H
authors.initials: H
authors.lastname: Wiebusch
authors.forename: A
authors.initials: A
authors.lastname: Enbergs
authors.forename: A
authors.initials: A
authors.lastname: Dorszewski
authors.forename: S
authors.initials: S
authors.lastname: Kerber
authors.forename: H
authors.initials: H
authors.lastname: Schulte
authors.forename: C
authors.initials: C
authors.lastname: Vielhauer
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
authors.forename: G
authors.initials: G
authors.lastname: Assmann
authors.forename: G
authors.initials: G
authors.lastname: Breithardt
authors.forename: H
authors.initials: H
authors.lastname: Funke
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005787:Gene Frequency; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012984:Software
chemical_list: D004247:DNA; D008049:Lipase; D008071:Lipoprotein Lipase