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The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

BACKGROUND: Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological con...

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Autores principales: Wung, Shu-Fen, Kulkarni, Medha V, Pullinger, Clive R, Malloy, Mary J, Kane, John P, Aouizerat, Bradley E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1538992/
https://www.ncbi.nlm.nih.gov/pubmed/16822320
http://dx.doi.org/10.1186/1476-511X-5-19
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author Wung, Shu-Fen
Kulkarni, Medha V
Pullinger, Clive R
Malloy, Mary J
Kane, John P
Aouizerat, Bradley E
author_facet Wung, Shu-Fen
Kulkarni, Medha V
Pullinger, Clive R
Malloy, Mary J
Kane, John P
Aouizerat, Bradley E
author_sort Wung, Shu-Fen
collection PubMed
description BACKGROUND: Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X) allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. RESULTS: We found evidence of significant allelic (447X(control): 0.130 vs. 447X(case): 0.031, χ(2 )= 29.085; 1df; p < 0.001) and genotypic association (SS: 0.745 vs. 0.939, and SX+XX: 0.255 vs. 0.061) in controls and cases, respectively (χ(2 )= 26.09; 1df; p < 0.001). In cases, depletion of the 447X allele is associated with a significant elevation in very-low-density lipoprotein cholesterol (VLDL-C, p = 0.045). Consonant with previous studies of this polymorphism, regression models predict that carriers of the 447X allele displayed significantly lower TG, low-density lipoprotein cholesterol (LDL-C) and TG/high-density lipoprotein cholesterol (HDL-C) ratio. CONCLUSION: These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.
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spelling pubmed-15389922006-08-11 The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion Wung, Shu-Fen Kulkarni, Medha V Pullinger, Clive R Malloy, Mary J Kane, John P Aouizerat, Bradley E Lipids Health Dis Research BACKGROUND: Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X) allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. RESULTS: We found evidence of significant allelic (447X(control): 0.130 vs. 447X(case): 0.031, χ(2 )= 29.085; 1df; p < 0.001) and genotypic association (SS: 0.745 vs. 0.939, and SX+XX: 0.255 vs. 0.061) in controls and cases, respectively (χ(2 )= 26.09; 1df; p < 0.001). In cases, depletion of the 447X allele is associated with a significant elevation in very-low-density lipoprotein cholesterol (VLDL-C, p = 0.045). Consonant with previous studies of this polymorphism, regression models predict that carriers of the 447X allele displayed significantly lower TG, low-density lipoprotein cholesterol (LDL-C) and TG/high-density lipoprotein cholesterol (HDL-C) ratio. CONCLUSION: These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors. BioMed Central 2006-07-05 /pmc/articles/PMC1538992/ /pubmed/16822320 http://dx.doi.org/10.1186/1476-511X-5-19 Text en Copyright © 2006 Wung et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wung, Shu-Fen
Kulkarni, Medha V
Pullinger, Clive R
Malloy, Mary J
Kane, John P
Aouizerat, Bradley E
The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title_full The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title_fullStr The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title_full_unstemmed The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title_short The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
title_sort lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1538992/
https://www.ncbi.nlm.nih.gov/pubmed/16822320
http://dx.doi.org/10.1186/1476-511X-5-19
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