Linkage of a candidate gene locus to familial combined hyperlipidemia - Lecithin: Cholesterol acyltransferase on 16q

B. E. Aouizerat, H. Allayee, R. M. Cantor, G. M. Dallinga-Thie, C. D. Lanning, T. W A De Bruin, A. J. Lusis, J. I. Rotter

Research output: Contribution to journalArticle

Abstract

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by elevated levels of plasma cholesterol and triglycerides that is present in 10% to 20% of patients with premature coronary artery disease. To study the pathophysiological basis and genetics of FCHL, we previously reported recruitment of 18 large families. We now report linkage studies of 14 candidate genes selected for their potential involvement in the aspects of lipid and lipoprotein metabolism that are altered in FCHL. We used highly polymorphic markers linked to the candidate genes, and these markers were analyzed using several complementary, nonparametric statistical allele-sharing linkage methodologies. This current sample has been extended over the one in which we identified an association with the apolipoprotein (apo) AI-CIII-AIV gene cluster. We observed evidence for linkage of this region and FCHL (P<0.001), providing additional support for its involvement in FCHL. We also identified a new locus showing significant evidence of linkage to the disorder: the lecithin:cholesterol acyltransferase (LCAT) locus (P<0.0006) on chromosome 16. In addition, analysis of the manganese superoxide dismutase locus on chromosome 6 revealed a suggestive linkage result in this sample (P<0.006). Quantitative traits related to FCHL also provided some evidence of linkage to these regions. No evidence of linkage to the lipoprotein lipase gene, the microsomal triglyceride transfer protein gene, or several other genes involved in lipid metabolism was observed. The data suggest that the lecithin:cholesterol acyltransferase and apolipoprotein AI-CIII-AIV loci may act as modifying genes contributing to the expression of FCHL.

Original languageEnglish (US)
Pages (from-to)2730-2736
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number11
DOIs
StatePublished - Jan 1 1999

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Keywords

  • Familial combined hyperlipidemia
  • Genetics
  • Lecithin:cholesterol acyltransferase
  • Lipid metabolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Aouizerat, B. E., Allayee, H., Cantor, R. M., Dallinga-Thie, G. M., Lanning, C. D., De Bruin, T. W. A., Lusis, A. J., & Rotter, J. I. (1999). Linkage of a candidate gene locus to familial combined hyperlipidemia - Lecithin: Cholesterol acyltransferase on 16q. Arteriosclerosis, Thrombosis, and Vascular Biology, 19(11), 2730-2736. https://doi.org/10.1161/01.ATV.19.11.2730