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Rare and common mutations in hyperlipidemia and atherosclerosis. With special reference to familial defective apolipoprotein B-100.
Scand J Clin Lab Invest Suppl. 1995; 220:57-76.SJ

Abstract

The aim was to identify genetic determinants for the development of hyperlipidemia and/or atherosclerosis. The present set of studies demonstrates for the first time the clinical expression (phenotype) of a newly discovered monogenic disorder named Familial Defective Apolipoprotein B-100 (FDB). FDB is caused by a G to A mutation in the binding protein (apolipoprotein B-100) for the cholesterol-rich low density lipoprotein (LDL), such that the affinity of LDL to the LDL receptor is severely reduced. In all 135 individuals with FDB from 56 families and 8 different countries, including Denmark, are described. On average, the effect of the FDB mutation was to increase plasma and LDL cholesterol in both men and women by about 3 mmol/l; at age 55 the average plasma cholesterol of men and women with FDB was 9.4 mmol/l and 8.9 mmol/l, respectively. A sharp rise in frequency of coronary artery disease as a function of age in both FDB males and females was comparable to that found in Familial Hypercholesterolemia (FH). At the age of 60, about 70% of both men and women with FDB had coronary artery disease; at the same age approximately 40% had tendon xanthomas, and 35% had arcus corneae, irrespective of gender. Surprisingly, the frequencies of arcus corneae were not strikingly higher than those found in the general population sample from the Copenhagen City Heart Study. Only few patients with FDB had xanthelasmas. Finally, the frequency of this mutation was estimated at 1/500-1/700 in the general population, which is equivalent to that of clinical FH. All in all the results suggest FDB to be a severe genetic disorder with early penetrance, associated with substantial elevations in plasma and LDL cholesterol and with an increased frequency of premature coronary artery disease and of tendon xanthomas. For comparison, a number of common polymorphisms in the 5'-flanking region of the insulin gene, in the apoB gene and in the apoAI-CIII-AIV gene cluster, associated with minor effects on hyperlipidemia and/or cardiovascular disease are also examined.

Authors+Show Affiliations

Department of Clinical Biochemistry, Rigshospitalet, National University Hospital of Denmark, Copenhagen.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

7652481

Citation

Tybjaerg-Hansen, A. "Rare and Common Mutations in Hyperlipidemia and Atherosclerosis. With Special Reference to Familial Defective Apolipoprotein B-100." Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum, vol. 220, 1995, pp. 57-76.
Tybjaerg-Hansen A. Rare and common mutations in hyperlipidemia and atherosclerosis. With special reference to familial defective apolipoprotein B-100. Scand J Clin Lab Invest Suppl. 1995;220:57-76.
Tybjaerg-Hansen, A. (1995). Rare and common mutations in hyperlipidemia and atherosclerosis. With special reference to familial defective apolipoprotein B-100. Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum, 220, 57-76.
Tybjaerg-Hansen A. Rare and Common Mutations in Hyperlipidemia and Atherosclerosis. With Special Reference to Familial Defective Apolipoprotein B-100. Scand J Clin Lab Invest Suppl. 1995;220:57-76. PubMed PMID: 7652481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rare and common mutations in hyperlipidemia and atherosclerosis. With special reference to familial defective apolipoprotein B-100. A1 - Tybjaerg-Hansen,A, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 57 EP - 76 JF - Scandinavian journal of clinical and laboratory investigation. Supplementum JO - Scand J Clin Lab Invest Suppl VL - 220 N2 - The aim was to identify genetic determinants for the development of hyperlipidemia and/or atherosclerosis. The present set of studies demonstrates for the first time the clinical expression (phenotype) of a newly discovered monogenic disorder named Familial Defective Apolipoprotein B-100 (FDB). FDB is caused by a G to A mutation in the binding protein (apolipoprotein B-100) for the cholesterol-rich low density lipoprotein (LDL), such that the affinity of LDL to the LDL receptor is severely reduced. In all 135 individuals with FDB from 56 families and 8 different countries, including Denmark, are described. On average, the effect of the FDB mutation was to increase plasma and LDL cholesterol in both men and women by about 3 mmol/l; at age 55 the average plasma cholesterol of men and women with FDB was 9.4 mmol/l and 8.9 mmol/l, respectively. A sharp rise in frequency of coronary artery disease as a function of age in both FDB males and females was comparable to that found in Familial Hypercholesterolemia (FH). At the age of 60, about 70% of both men and women with FDB had coronary artery disease; at the same age approximately 40% had tendon xanthomas, and 35% had arcus corneae, irrespective of gender. Surprisingly, the frequencies of arcus corneae were not strikingly higher than those found in the general population sample from the Copenhagen City Heart Study. Only few patients with FDB had xanthelasmas. Finally, the frequency of this mutation was estimated at 1/500-1/700 in the general population, which is equivalent to that of clinical FH. All in all the results suggest FDB to be a severe genetic disorder with early penetrance, associated with substantial elevations in plasma and LDL cholesterol and with an increased frequency of premature coronary artery disease and of tendon xanthomas. For comparison, a number of common polymorphisms in the 5'-flanking region of the insulin gene, in the apoB gene and in the apoAI-CIII-AIV gene cluster, associated with minor effects on hyperlipidemia and/or cardiovascular disease are also examined. SN - 0085-591X UR - https://www.unboundmedicine.com/medline/citation/7652481/Rare_and_common_mutations_in_hyperlipidemia_and_atherosclerosis__With_special_reference_to_familial_defective_apolipoprotein_B_100_ L2 - http://www.diseaseinfosearch.org/result/2166 DB - PRIME DP - Unbound Medicine ER -
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