Genetics and kinetics of familial hypercholesterolemia, with the special focus on FH-(Marburg) p.W556R

Atherosclerosis. Supplements
Muhidien SoufiJuergen R Schaefer

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder, caused by mutations in the low density lipoprotein receptor (LDLR) gene. FH is characterized by elevated plasma LDL cholesterol, premature atherosclerosis and high risk of premature myocardial infarction. Extended work has been done to understand both, the primary genetic defect as well as the in vivo kinetic consequences of this disease. Both approaches, genetics and kinetics, are challenging but also fruitful approaches for a better understanding of this devastating disease. For this we reviewed the recent literature and used our in vitro and in vivo data on one of the most frequently occurring types of FH, the FH(Marburg) p.W556R. To identify the primary genetic defect of the FH(Marburg) we used denaturing gradient gel electrophoresis (DGGE) mutation analysis. In vivo kinetic studies were performed in a heterozygote FH(Marburg) subject and in 5 healthy control subjects utilizing a stable isotope tracer kinetic approach with 3D-leucine. DGGE screening of the LDLR gene identified a tryptophan (W) to arginine (R) substitution at residue 556 (p.W556R) in the fifth conserved YWTD repeat of the LDLR-beta-propeller in FH(Marburg). In vivo kinetic studie...Continue Reading

References

Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
May 1, 1989·Circulation·G A Reynolds
Apr 4, 1986·Science·M S Brown, J L Goldstein
Jul 19, 2002·Human Mutation·Ludovic VillégerMathilde Varret
May 16, 2003·Lancet·J Zschocke, J R Schaefer
May 12, 2004·Atherosclerosis·Muhidien SoufiJuergen R Schaefer
Aug 24, 2004·American Journal of Epidemiology·Melissa A AustinSteve E Humphries
Jan 8, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·John S MillarDaniel J Rader
Apr 13, 2005·Atherosclerosis·M Mert SözenSteve E Humphries

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Citations

Apr 25, 2012·Clinical Research in Cardiology Supplements·Juergen R SchaeferMuhidien Soufi
Oct 25, 2011·Journal of Paediatrics and Child Health·Robert N Justo
Jul 6, 2014·Annals of Pediatric Cardiology·Mithun J Varghese
Mar 9, 2012·Atherosclerosis·Frederick J Raal, Raul D Santos
Jun 17, 2015·The American Journal of Forensic Medicine and Pathology·Steffen HeideMuhidin Soufi

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