Molecular genetic study of Finns with hypoalphalipoproteinemia and hyperalphalipoproteinemia: a novel Gly230 Arg mutation (LCAT[Fin]) of lecithin:cholesterol acyltransferase (LCAT) accounts for 5% of cases with very low serum HDL cholesterol levels

Arteriosclerosis, Thrombosis, and Vascular Biology
H E MiettinenK Kontula

Abstract

In an attempt to identify genetic factors underlying extreme alterations of serum HDL cholesterol (HDL-C) concentrations, we examined two probands with HDL-C levels <0.2 mmol/L and subsequently screened two large cohorts of smoking men, one with very low (0.2 to 0.7 mmol/L, n=156) and the other with elevated (1.9 to 3.6 mmol/L, n=160) HDL-C levels, for the newly detected mutations as well as some other mutations proposed to affect HDL-C levels. One of the probands had corneal opacities, microalbuminuria, hypertriglyceridemia, and reduced LDL apoprotein B concentration; the other had anemia and presented with stomatocytosis in his peripheral blood. The first proband was found to be homozygous for a novel LCAT Gly230Arg (LCAT[Fin]) mutation, and the second was homozygous for an Arg399Cys mutation we described previously. Transient expression of the mutant LCAT(Fin) cDNA in COS cells disclosed markedly diminished LCAT enzyme activity. In the low-HDL-C group of men (n=156), 8 carriers of LCAT(Fin) and 1 carrier of the LCAT Arg399Cys were identified. In addition, the frequency of the lipoprotein lipase (LPL) Asn291Ser mutation was significantly (P<.05) higher in the low-HDL-C group (4.8%) than in the high-HDL-C group (1.6%). In addi...Continue Reading

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Citations

May 9, 2012·Journal of Lipid Research·Sandra Kunnen, Miranda Van Eck
May 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Anne BraunMonty Krieger
Mar 3, 2015·Nature Communications·Alisa GlukhovaJohn J G Tesmer
Dec 29, 2006·Journal of Lipid Research·Wim A van der SteegJan Albert Kuivenhoven
Oct 13, 2006·The Journal of Biological Chemistry·Bassam HaidarYves L Marcel
Jul 13, 2012·Journal of Atherosclerosis and Thrombosis·Erina ShigematsuYasuo Terauchi
Jul 15, 2021·Lipids in Health and Disease·Roopa MehtaCarlos A Aguilar-Salinas
May 12, 2009·Metabolism: Clinical and Experimental·Wanee PlengpanichWeerapan Khovidhunkit

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