Abstract
ApolipoproteinB 100 (apoB-100) is an important component of atherogenic lipoproteins
such as LDL and serves as a ligand for the LDL-receptor. Familial defective apolipoproteinB
100 (FDB) is caused by a R3500Q mutation of the apoB gene and results in decreased
binding of LDL to the LDL-receptor. So far FDB is the most frequent and best studied
alteration of apoB-100. Apart from this, three other apoB mutations, R3500W, R3531C
and R3480W, affecting binding to the LDL-receptor are known to date. We screened the
apoB gene segment of codons 3448–3561 by denaturing gradient gel electrophoresis (DGGE)
analysis in a total of 853 consecutively sampled German patients undergoing diagnostic
coronary angiography for suspected CAD. By this, a new single base mutation was detected
and confirmed by DNA sequencing. The mutation, CAC3543TAC results in a His3543Tyr substitution in apoB-100 (H3543Y). The prevalence of heterozygotes
for H3543Y in the study population was 0.47% compared to 0.12% for the known Arg 3500
Gln (R3500Q) mutation. In conclusion, the new mutation is four times more frequent
than “classical” FDB and thus appears to be the most common apoB mutation in Germany.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A receptor-mediated pathway for cholesterol homeostasis.Science. 1986; 232: 34-47
- Familial defective apolipoprotein B-100: a single mutation that causes hypercholesterolemia and premature coronary artery disease.Atherosclerosis. 1992; 96: 91-107
- Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100.Proc. Natl. Acad. Sci. U.S.A. 1989; 86: 587-591
- The apolipoprotein B R3531C mutation. Characteristics of 24 subjects from 9 kindreds.J. Lipid Res. 1999; 40: 318-327
- Independent mutations at codon 3500 of the apolipoprotein B gene are associated with hyperlipidemia.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1025-1029
- Familial ligand-defective apolipoprotien B. Identification of a new mutation that decreases LDL receptor binding affinity.J. Clin. Invest. 1995; 95: 1225-1234
- The affinity of low-density lipoproteins and of very-low-density lipoprotein remnants for the low-density lipoprotein receptor in homozygous familial defective apolipoprotein B-100.Atherosclerosis. 1995; 115: 263-272
- Mutations in the apolipoprotein (apo) B-100 receptor-binding region: detection of apoB-100 (Arg 3500 → Trp) associated with two new haplotypes and evidence that apoB-100 (Glu3405 → Gln) diminishes receptor-mediated uptake of LDL.Clin. Chem. 1999; 45: 1026-1038
- Accumulation of “small dense” low density lipoproteins (LDL) in a homozygous patients with familial defective apolipoprotein B-100 results from heterogenous interaction of LDL subfractions with the LDL receptor.J. Clin. Invest. 1993; 92: 2922-2933
- Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease.N. Engl. J. Med. 1998; 338: 1577-1584
- Identification and haplotype analysis of apolipoprotein B-100 Arg3500 → Trp mutation in hyperlipidemic Chinese.Chin. Clin. Chem. 1998; 44: 1659-1665
- Familial defective apolipoprotein B-100: haplotype analysis of the arginine(3500) glutamine mutation.Atherosclerosis. 1991; 88: 219-226
- Haplotype analysis of the human apolipoprotein B mutation associated with familial defective apolipoprotein B100.Am. J. Human Genet. 1990; 47: 712-720
- High prevalence of FDB3500 mutation in the Swiss population.Atherosclerosis. 2000; 153: 519-521
- Clinically applicable mutation screening in familial hypercholesterolemia.Human Mutat. 1996; 8: 168-177
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin. Chem. 1972; 18: 499-502
- Modification of the melting properties of duplex DNA by attachment of a GC-rich DNA sequence as determined by denaturing gradient gel electrophoresis.Nucl. Acids Res. 1985; 13: 3111-3129
- Detection of the apoB-3500 mutation (glutamine for arginine) by gene amplification and cleavage with MspI.J. Lipid Res. 1991; 32: 1229-1233
- Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding.Proc. Natl. Acad. Sci. U.S.A. 1987; 84: 6919-6923
- Homozygous familial defective apolipoprotein B-100. Enhanced removal of apolipoprotein E-containing VLDLs and decreased production of LDLs.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 348-353
- The effect of the apolipoprotein E polymorphism on lipid levels in patients with familial defective apolipoprotein B-100.Clin. Invest. 1993; 71: 277-280
- Association of mutations in the apolipoprotein B gene with hypercholesterolemia and the risk of ischemic heart disease (letter).N. Engl. J. Med. 1998; 339: 1641-1642
- Comparison of apolipoprotein B metabolism in familial defective apolipoprotein B and heterogeneous familial hypercholesterolemia.Atherosclerosis. 2002; 162: 33-43
- Familial defective apolipoprotein B-100: mild hypercholesterolaemia without atherosclerosis in a homozygous patient.Lancet. 1992; 340: 1362
- Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100.J. Clin. Invest. 1998; 101: 1084-1093
- Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding.J. Clin. Invest. 1998; 101: 2658-2664
- Familial defective apolipoprotein B-100: detection in the United Kingdom and Scandinavia, and clinical characteristics of ten cases.Atherosclerosis. 1990; 80: 235-242
- The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia.Atherosclerosis. 2002; 165: 127-135
- Rationale and design of the LURIC study—a resource for functional genomics pharmacogenomics and long-term prognosis of cardiovascular disease (review).Pharmacogenomics. 2001; 2: S1-S73
- The molecular mechanism for the genetic disorder familial defective apolipoprotein B100.J. Biol. Chem. 2001; 276: 9214-9218
- Well-defined regions of apolipoprotein B-100 undergo conformational change during its intravascular metabolism.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1301-1308
Article info
Publication history
Accepted:
December 19,
2003
Received:
July 29,
2003
Identification
Copyright
© 2004 Published by Elsevier Inc.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Corrigendum to “A new but frequent mutation of apoB-100—apoB His3543Tyr” [Atherosclerosis 2004;174(1):11–16]AtherosclerosisVol. 178Issue 2
