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Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.
J Lipid Res. 2000 Feb; 41(2):245-52.JL

Abstract

Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1-2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL-cholesterol levels and that a polymorphism within the HL promoter (-514C-->T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The -514C-->T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors.

Authors+Show Affiliations

Department of Microbiology, University of California, Los Angeles, CA 90095, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10681408

Citation

Allayee, H, et al. "Contribution of the Hepatic Lipase Gene to the Atherogenic Lipoprotein Phenotype in Familial Combined Hyperlipidemia." Journal of Lipid Research, vol. 41, no. 2, 2000, pp. 245-52.
Allayee H, Dominguez KM, Aouizerat BE, et al. Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia. J Lipid Res. 2000;41(2):245-52.
Allayee, H., Dominguez, K. M., Aouizerat, B. E., Krauss, R. M., Rotter, J. I., Lu, J., Cantor, R. M., de Bruin, T. W., & Lusis, A. J. (2000). Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia. Journal of Lipid Research, 41(2), 245-52.
Allayee H, et al. Contribution of the Hepatic Lipase Gene to the Atherogenic Lipoprotein Phenotype in Familial Combined Hyperlipidemia. J Lipid Res. 2000;41(2):245-52. PubMed PMID: 10681408.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia. AU - Allayee,H, AU - Dominguez,K M, AU - Aouizerat,B E, AU - Krauss,R M, AU - Rotter,J I, AU - Lu,J, AU - Cantor,R M, AU - de Bruin,T W, AU - Lusis,A J, PY - 2000/2/19/pubmed PY - 2000/4/29/medline PY - 2000/2/19/entrez SP - 245 EP - 52 JF - Journal of lipid research JO - J Lipid Res VL - 41 IS - 2 N2 - Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1-2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL-cholesterol levels and that a polymorphism within the HL promoter (-514C-->T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The -514C-->T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors. SN - 0022-2275 UR - https://www.unboundmedicine.com/medline/citation/10681408/Contribution_of_the_hepatic_lipase_gene_to_the_atherogenic_lipoprotein_phenotype_in_familial_combined_hyperlipidemia_ L2 - http://www.jlr.org/cgi/pmidlookup?view=long&amp;pmid=10681408 DB - PRIME DP - Unbound Medicine ER -