Contribution of mutations in low density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) genes to familial combined hyperlipidemia (FCHL): a reappraisal by using a resequencing approach

Atherosclerosis
Ilenia MinicocciMarcello Arca

Abstract

Defective low-density lipoprotein receptor (LDLR) and lipoprotein lipase (LPL) alleles have been implicated in familial combined hyperlipidemia (FCHL). However, their contribution might have been influenced by diagnostic criteria. This study was aimed to reassess the frequency of rare and common variants in LDLR and LPL in FCHL individuals classified with stringent criteria. LDLR and LPL were resequenced in 208 FHCL and 171 controls. Variants were classified as loss- (LOF) or gain-of-function (GOF) based upon in silico prediction, familial segregation and available functional data. Eight LOF variants were detected in LDLR, 6 of which were missense and 2 were predicted to disrupt normal splicing; all were present at heterozygous state. They were found in 10 FCHL but not in controls, thus indicating that 4.8% of FCHL individuals should be reclassified as FH. LDL-C (positive) and BMI (negative) were the strongest predictors of LDLR mutations with LDL-C 181 mg/dl being the best threshold for diagnosing the presence of dysfunctional LDLR alleles. The cumulative prevalence of definite LPL defective alleles (1 rare and 2 common heterozygous missense variants) was comparable between FCHL and controls (10.1% vs. 10.5%). Conversely, the ...Continue Reading

References

Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
Oct 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·S P BabirakJ D Brunzell
Aug 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·E GagnéM R Hayden
Jan 1, 1994·The Clinical Investigator·M SeedS E Humphries
Jun 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·D N NevinS S Deeb
Aug 1, 1996·European Journal of Clinical Investigation·T W de BruinS E Humphries
Nov 28, 2002·Journal of Lipid Research·Martin MerkelIra J Goldberg
Sep 6, 2003·Atherosclerosis·H A W NeilUNKNOWN Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee
Feb 7, 2004·Human Molecular Genetics·C C ShouldersR P Naoumova
Mar 3, 2004·Nature Genetics·Päivi PajukantaLeena Peltonen
Aug 7, 2004·Science·Jonathan C CohenHelen H Hobbs
Oct 27, 2005·Human Mutation·Sigrid W FouchierJoep C Defesche
Apr 1, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Jaap RipJan Albert Kuivenhoven
Jan 24, 2007·Neurobiology of Aging·R LämsäH Soininen
Mar 16, 2007·American Journal of Human Genetics·Gregory V KryukovShamil R Sunyaev
Aug 25, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Jian WangRobert A Hegele
Nov 15, 2008·Journal of the American College of Cardiology·Gail P JarvikArno G Motulsky
Jun 5, 2012·The Journal of Clinical Endocrinology and Metabolism·Ilenia MinicocciMarcello Arca
Mar 19, 2014·Journal of the American College of Cardiology·Allan D SnidermanSergio Fazio

❮ Previous
Next ❯

Citations

Dec 29, 2015·Current Opinion in Lipidology·Amanda J Brahm, Robert A Hegele
Feb 6, 2017·Current Opinion in Lipidology·Paul N Hopkins, Stacey R Lane
Apr 5, 2016·Journal of Lipid Research·Ilenia MinicocciMarcello Arca
Dec 18, 2018·Journal of Cellular Biochemistry·Eskandar TaghizadehSeyed Mohammad Gheibi Hayat
Oct 11, 2019·BioFactors·Eskandar TaghizadehAlireza Pasdar
Nov 15, 2019·IUBMB Life·Eskandar TaghizadehAlireza Pasdar
Mar 28, 2021·Scientific Reports·A M BeaI Lamiquiz-Moneo
Sep 4, 2021·Biochemical Genetics·Eskandar TaghizadehSeyed Mohammad Gheibihayat

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.