Atherosclerosis
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Comparative Study Clinical Trial Controlled Clinical Trial
Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography.
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. ⋯ 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.
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Progress is slow in the integration of coronary heart disease prevention into daily clinical practice by cardiologists and other physicians working in cardiology, internal medicine and primary healthcare. This is not due to a lack of professional recommendations on coronary prevention. ⋯ The most recent recommendations from the Joint Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension reinforce the importance of secondary prevention and how they can be extended to primary prevention by targeting high-risk individuals in the general population. It is hoped that development of guidelines at a national level will ensure a common approach to coronary heart disease prevention throughout Europe.
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The phenotypic expression of heterozygous familial hypercholesterolemia (FH) is variable form biochemical and clinical standpoints and several genetic and environmental factors could contribute to explain this variability. We have compared, in a cohort of 266 heterozygous FH children and adolescents (1-19 years), the variation in plasma lipoprotein-lipid levels among patients defined by three mutations in the low density lipoprotein receptor (LDLR) gene. Comparison of the plasma total and LDL-cholesterol (LDL-C) levels among the three mutation groups revealed significant differences. ⋯ In conclusion, the present study demonstrated that the overall contribution of age to variation in the lipoprotein profile of heterozygous FH children is similar to the effect observed among healthy children. The effect of LDLR gene in FH is dominant and there was no difference in plasma TC and LDL-C due to gender. Finally, this study indicates that the LDLR gene type mutations are a modulator of the magnitude of the increase in plasma TC and LDL-C levels noted among FH heterozygote children.
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Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus is related to the occurrence of premature coronary artery disease. Two restriction fragment length polymorphisms, revealed by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb), H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. ⋯ The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic lipase gene locus were also studied in the same groups of subjects. These showed no differences between cases and controls. We conclude that DNA variation at or adjacent to the lipoprotein lipase gene may contain genetic determinants for the occurrence of premature coronary artery disease.