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Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups
The apolipoprotein E-C1-C4-C2 gene cluster at 19q13.32 encodes four amphipathic apolipoproteins. The influence of APOE common polymorphisms on plasma lipid/lipoprotein profile, especially on LDL-related traits, is well recognized; however, little is known about the role of other genes/variants in th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435132/ https://www.ncbi.nlm.nih.gov/pubmed/30913229 http://dx.doi.org/10.1371/journal.pone.0214060 |
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author | Pirim, Dilek Radwan, Zaheda H. Wang, Xingbin Niemsiri, Vipavee Hokanson, John E. Hamman, Richard F. Feingold, Eleanor Bunker, Clareann H. Demirci, F. Yesim Kamboh, M. Ilyas |
author_facet | Pirim, Dilek Radwan, Zaheda H. Wang, Xingbin Niemsiri, Vipavee Hokanson, John E. Hamman, Richard F. Feingold, Eleanor Bunker, Clareann H. Demirci, F. Yesim Kamboh, M. Ilyas |
author_sort | Pirim, Dilek |
collection | PubMed |
description | The apolipoprotein E-C1-C4-C2 gene cluster at 19q13.32 encodes four amphipathic apolipoproteins. The influence of APOE common polymorphisms on plasma lipid/lipoprotein profile, especially on LDL-related traits, is well recognized; however, little is known about the role of other genes/variants in this gene cluster. In this study, we evaluated the role of common and uncommon/rare genetic variation in this gene region on inter-individual variation in plasma lipoprotein levels in non-Hispanic Whites (NHWs) and African blacks (ABs). In the variant discovery step, the APOE, APOC1, APOC4, APOC2 genes were sequenced along with their flanking and hepatic control regions (HCR1 and HCR2) in 190 subjects with extreme HDL-C/TG levels. The next step involved the genotyping of 623 NHWs and 788 ABs for the identified uncommon/rare variants and common tagSNPs along with additional relevant SNPs selected from public resources, followed by association analyses with lipid traits. A total of 230 sequence variants, including 15 indels were identified, of which 65 were novel. A total of 70 QC-passed variants in NHWs and 108 QC-passed variants in ABs were included in the final association analyses. Single-site association analysis of SNPs with MAF>1% revealed 20 variants in NHWs and 24 variants in ABs showing evidence of association with at least one lipid trait, including several variants exhibiting independent associations from the established APOE polymorphism even after multiple-testing correction. Overall, our study has confirmed known associations and also identified novel associations in this genomic region with various lipid traits. Our data also support the contribution of both common and uncommon/rare variation in this gene region in affecting plasma lipid profile in the general population. |
format | Online Article Text |
id | pubmed-6435132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64351322019-04-08 Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups Pirim, Dilek Radwan, Zaheda H. Wang, Xingbin Niemsiri, Vipavee Hokanson, John E. Hamman, Richard F. Feingold, Eleanor Bunker, Clareann H. Demirci, F. Yesim Kamboh, M. Ilyas PLoS One Research Article The apolipoprotein E-C1-C4-C2 gene cluster at 19q13.32 encodes four amphipathic apolipoproteins. The influence of APOE common polymorphisms on plasma lipid/lipoprotein profile, especially on LDL-related traits, is well recognized; however, little is known about the role of other genes/variants in this gene cluster. In this study, we evaluated the role of common and uncommon/rare genetic variation in this gene region on inter-individual variation in plasma lipoprotein levels in non-Hispanic Whites (NHWs) and African blacks (ABs). In the variant discovery step, the APOE, APOC1, APOC4, APOC2 genes were sequenced along with their flanking and hepatic control regions (HCR1 and HCR2) in 190 subjects with extreme HDL-C/TG levels. The next step involved the genotyping of 623 NHWs and 788 ABs for the identified uncommon/rare variants and common tagSNPs along with additional relevant SNPs selected from public resources, followed by association analyses with lipid traits. A total of 230 sequence variants, including 15 indels were identified, of which 65 were novel. A total of 70 QC-passed variants in NHWs and 108 QC-passed variants in ABs were included in the final association analyses. Single-site association analysis of SNPs with MAF>1% revealed 20 variants in NHWs and 24 variants in ABs showing evidence of association with at least one lipid trait, including several variants exhibiting independent associations from the established APOE polymorphism even after multiple-testing correction. Overall, our study has confirmed known associations and also identified novel associations in this genomic region with various lipid traits. Our data also support the contribution of both common and uncommon/rare variation in this gene region in affecting plasma lipid profile in the general population. Public Library of Science 2019-03-26 /pmc/articles/PMC6435132/ /pubmed/30913229 http://dx.doi.org/10.1371/journal.pone.0214060 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Pirim, Dilek Radwan, Zaheda H. Wang, Xingbin Niemsiri, Vipavee Hokanson, John E. Hamman, Richard F. Feingold, Eleanor Bunker, Clareann H. Demirci, F. Yesim Kamboh, M. Ilyas Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title | Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title_full | Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title_fullStr | Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title_full_unstemmed | Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title_short | Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
title_sort | apolipoprotein e-c1-c4-c2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435132/ https://www.ncbi.nlm.nih.gov/pubmed/30913229 http://dx.doi.org/10.1371/journal.pone.0214060 |
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