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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0214060 |
| _version_ | 1798032714220175360 |
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| author | Dilek Pirim Zaheda H Radwan Xingbin Wang Vipavee Niemsiri John E Hokanson Richard F Hamman Eleanor Feingold Clareann H Bunker F Yesim Demirci M Ilyas Kamboh |
| author_facet | Dilek Pirim Zaheda H Radwan Xingbin Wang Vipavee Niemsiri John E Hokanson Richard F Hamman Eleanor Feingold Clareann H Bunker F Yesim Demirci M Ilyas Kamboh |
| author_sort | Dilek Pirim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T20:18:11Z |
| format | Article |
| id | doaj.art-9dd29a19038b48b486e15b0bf8622cc0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T20:18:11Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9dd29a19038b48b486e15b0bf8622cc02022-12-22T04:04:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021406010.1371/journal.pone.0214060Apolipoprotein E-C1-C4-C2 gene cluster region and inter-individual variation in plasma lipoprotein levels: a comprehensive genetic association study in two ethnic groups.Dilek PirimZaheda H RadwanXingbin WangVipavee NiemsiriJohn E HokansonRichard F HammanEleanor FeingoldClareann H BunkerF Yesim DemirciM Ilyas KambohThe 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.https://doi.org/10.1371/journal.pone.0214060 |
| spellingShingle | Dilek Pirim Zaheda H Radwan Xingbin Wang Vipavee Niemsiri John E Hokanson Richard F Hamman Eleanor Feingold Clareann H Bunker F Yesim Demirci M Ilyas Kamboh 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. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0214060 |
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