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Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk
This study is expected to investigate the association of ATP/GTP binding protein-like 4 (AGBL4), LDL receptor related protein 8 (LRP8) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene single nucleotide variants (SNVs) with lipid metabolism in 2,552 individuals (Jing, 1,272 and Han, 1,2...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112603/ https://www.ncbi.nlm.nih.gov/pubmed/27853278 http://dx.doi.org/10.1038/srep37375 |
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author | Guo, Tao Yin, Rui-Xing Yao, Li-Mei Huang, Feng Pan, Ling Lin, Wei-Xiong Yang, De-Zhai Pan, Shang-Ling |
author_facet | Guo, Tao Yin, Rui-Xing Yao, Li-Mei Huang, Feng Pan, Ling Lin, Wei-Xiong Yang, De-Zhai Pan, Shang-Ling |
author_sort | Guo, Tao |
collection | PubMed |
description | This study is expected to investigate the association of ATP/GTP binding protein-like 4 (AGBL4), LDL receptor related protein 8 (LRP8) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene single nucleotide variants (SNVs) with lipid metabolism in 2,552 individuals (Jing, 1,272 and Han, 1,280). We identified 12 mutations in this motif. The genotype and allele frequencies of these variants were different between the two populations. Multiple-locus linkage disequilibrium (LD) elucidated the detected sites are not statistically independent. Possible integrative haplotypes and gene-by-gene (G × G) interactions, comprising mutations of the AGBL4, LRP8 and PCSK9 associated with total cholesterol (TC, AGBL4 G-G-A, PCSK9 C-G-A-A and G-G-A-A-C-A-T-T-T-G-G-A), triglyceride (TG, AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL cholesterol (HDL-C, AGBL4 A-A-G and A-A-G-A-A-G-T-C-C-A-A-G) and the apolipoprotein(Apo)A1/ApoB ratio (A1/B, PCSK9 C-A-A-G) in Jing minority. However, in the Hans, with TG (AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL-C (LRP8 A-A-G-T-C), LDL-C (LRP8 A-A-G-T-C and A-A-G-A-A-G-T-C-C-A-A-G) and A1/B (LRP8 A-C-A-T-T and PCSK9 C-A-A-G). Association analysis based on haplotype clusters and G × G interactions probably increased power over single-locus tests especially for TG. |
format | Online Article Text |
id | pubmed-5112603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51126032016-11-25 Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk Guo, Tao Yin, Rui-Xing Yao, Li-Mei Huang, Feng Pan, Ling Lin, Wei-Xiong Yang, De-Zhai Pan, Shang-Ling Sci Rep Article This study is expected to investigate the association of ATP/GTP binding protein-like 4 (AGBL4), LDL receptor related protein 8 (LRP8) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene single nucleotide variants (SNVs) with lipid metabolism in 2,552 individuals (Jing, 1,272 and Han, 1,280). We identified 12 mutations in this motif. The genotype and allele frequencies of these variants were different between the two populations. Multiple-locus linkage disequilibrium (LD) elucidated the detected sites are not statistically independent. Possible integrative haplotypes and gene-by-gene (G × G) interactions, comprising mutations of the AGBL4, LRP8 and PCSK9 associated with total cholesterol (TC, AGBL4 G-G-A, PCSK9 C-G-A-A and G-G-A-A-C-A-T-T-T-G-G-A), triglyceride (TG, AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL cholesterol (HDL-C, AGBL4 A-A-G and A-A-G-A-A-G-T-C-C-A-A-G) and the apolipoprotein(Apo)A1/ApoB ratio (A1/B, PCSK9 C-A-A-G) in Jing minority. However, in the Hans, with TG (AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL-C (LRP8 A-A-G-T-C), LDL-C (LRP8 A-A-G-T-C and A-A-G-A-A-G-T-C-C-A-A-G) and A1/B (LRP8 A-C-A-T-T and PCSK9 C-A-A-G). Association analysis based on haplotype clusters and G × G interactions probably increased power over single-locus tests especially for TG. Nature Publishing Group 2016-11-17 /pmc/articles/PMC5112603/ /pubmed/27853278 http://dx.doi.org/10.1038/srep37375 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Guo, Tao Yin, Rui-Xing Yao, Li-Mei Huang, Feng Pan, Ling Lin, Wei-Xiong Yang, De-Zhai Pan, Shang-Ling Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title | Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title_full | Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title_fullStr | Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title_full_unstemmed | Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title_short | Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk |
title_sort | integrative mutation, haplotype and g × g interaction evidence connects abgl4, lrp8 and pcsk9 genes to cardiometabolic risk |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112603/ https://www.ncbi.nlm.nih.gov/pubmed/27853278 http://dx.doi.org/10.1038/srep37375 |
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