Low density lipoprotein receptor mutations in a selected population of individuals with moderate hypercholesterolemia

Atherosclerosis
M Arca, E Jokinen

Abstract

To evaluate mutations in the low density lipoprotein receptor (LDL-R) gene in moderate primary hypercholesterolemia, a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequencing, was used to screen the LDL-R gene in a selected population of 82 unrelated individuals with moderate elevation of plasma LDL-C [mean 4.55 +/- 0.55 mmol/l (176.4 +/- 21.6 mg/dl)]. Four subjects (5%) were found to be heterozygotes for missense mutations in the LDL-R gene. These mutations were located in four different exons (exons 6, 7, 15 and 17) and all alters highly conserved residues of LDL-R protein. None of these mutations were detected in 79 normocholesterolemic individuals. The mutation in exon 15 (T705I) was previously reported in a compound heterozygote for familial hypercholesterolemia (FH). In the proband carrying the mutation in exon 17 (R793Q), an in vivo LDL turnover study was performed and it demonstrated a reduction of LDL catabolism. These findings demonstrate that mutations in the LDL-R may occur in primary moderate hypercholesterolemia. They also extend the concept that some FH patients may present with a mild phenotype.

References

Jan 1, 1992·Human Mutation·H H HobbsJ L Goldstein
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Nov 1, 1985·American Journal of Medical Genetics·J J NoraD W Bilheimer
Feb 9, 1994·JAMA : the Journal of the American Medical Association·M ArcaS M Grundy

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Citations

Oct 27, 2005·Human Mutation·Sigrid W FouchierJoep C Defesche
Apr 15, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·S C HuntM E Samuels
Aug 2, 2003·Journal of Inherited Metabolic Disease·S Tonstad

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