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A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia
Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15)...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Springer-Verlag
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793376/ https://www.ncbi.nlm.nih.gov/pubmed/19816713 http://dx.doi.org/10.1007/s00439-009-0749-z |
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author | Huertas-Vazquez, Adriana Plaisier, Christopher L. Geng, Ruishuang Haas, Blake E. Lee, Jenny Greevenbroek, Marleen M. van der Kallen, Carla de Bruin, Tjerk W. A. Taskinen, Marja-Riitta Alagramam, Kumar N. Pajukanta, Päivi |
author_facet | Huertas-Vazquez, Adriana Plaisier, Christopher L. Geng, Ruishuang Haas, Blake E. Lee, Jenny Greevenbroek, Marleen M. van der Kallen, Carla de Bruin, Tjerk W. A. Taskinen, Marja-Riitta Alagramam, Kumar N. Pajukanta, Päivi |
author_sort | Huertas-Vazquez, Adriana |
collection | PubMed |
description | Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a significant association with any lipid-related trait. We investigated the expression of PCDH15 in different human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15(av-Tg) and Pcdh15(av-3J)) to investigate possible abnormalities in their lipid profile. We observed a significant difference in plasma TG and TC concentrations for the Pcdh15(av-3J) carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities. |
format | Text |
id | pubmed-2793376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-27933762009-12-29 A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia Huertas-Vazquez, Adriana Plaisier, Christopher L. Geng, Ruishuang Haas, Blake E. Lee, Jenny Greevenbroek, Marleen M. van der Kallen, Carla de Bruin, Tjerk W. A. Taskinen, Marja-Riitta Alagramam, Kumar N. Pajukanta, Päivi Hum Genet Original Investigation Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by the presence of multiple lipoprotein phenotypes that increase the risk of premature coronary heart disease. In a previous study, we identified an intragenic microsatellite marker within the protocadherin 15 (PCDH15) gene to be associated with high triglycerides (TGs) in Finnish dyslipidemic families. In this study we analyzed all four known nonsynonymous SNPs within PCDH15 in 1,268 individuals from Finnish and Dutch multigenerational families with FCHL. Association analyses of quantitative traits for SNPs were performed using the QTDT test. The nonsynonymous SNP rs10825269 resulted in a P = 0.0006 for the quantitative TG trait. Additional evidence for association was observed with the same SNP for apolipoprotein B levels (apo-B) (P = 0.0001) and total cholesterol (TC) levels (P = 0.001). None of the other three SNPs tested showed a significant association with any lipid-related trait. We investigated the expression of PCDH15 in different human tissues and observed that PCDH15 is expressed in several tissues including liver and pancreas. In addition, we measured the plasma lipid levels in mice with loss-of-function mutations in Pcdh15 (Pcdh15(av-Tg) and Pcdh15(av-3J)) to investigate possible abnormalities in their lipid profile. We observed a significant difference in plasma TG and TC concentrations for the Pcdh15(av-3J) carriers when compared with the wild type (P = 0.013 and P = 0.044, respectively). Our study suggests that PCDH15 is associated with lipid abnormalities. Springer-Verlag 2009-10-09 2010 /pmc/articles/PMC2793376/ /pubmed/19816713 http://dx.doi.org/10.1007/s00439-009-0749-z Text en © The Author(s) 2009 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Investigation Huertas-Vazquez, Adriana Plaisier, Christopher L. Geng, Ruishuang Haas, Blake E. Lee, Jenny Greevenbroek, Marleen M. van der Kallen, Carla de Bruin, Tjerk W. A. Taskinen, Marja-Riitta Alagramam, Kumar N. Pajukanta, Päivi A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title | A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title_full | A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title_fullStr | A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title_full_unstemmed | A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title_short | A nonsynonymous SNP within PCDH15 is associated with lipid traits in familial combined hyperlipidemia |
title_sort | nonsynonymous snp within pcdh15 is associated with lipid traits in familial combined hyperlipidemia |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793376/ https://www.ncbi.nlm.nih.gov/pubmed/19816713 http://dx.doi.org/10.1007/s00439-009-0749-z |
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