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Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity
Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to f...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587614/ https://www.ncbi.nlm.nih.gov/pubmed/23469169 http://dx.doi.org/10.1371/journal.pone.0056119 |
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author | Chung, Chia-Min Wang, Ruey-Yun Fann, Cathy S. J. Chen, Jaw-Wen Jong, Yuh-Shiun Jou, Yuh-Shan Yang, Hsin-Chou Kang, Chih-Sen Chen, Chien-Chung Chang, Huan-Cheng Pan, Wen-Harn |
author_facet | Chung, Chia-Min Wang, Ruey-Yun Fann, Cathy S. J. Chen, Jaw-Wen Jong, Yuh-Shiun Jou, Yuh-Shan Yang, Hsin-Chou Kang, Chih-Sen Chen, Chien-Chung Chang, Huan-Cheng Pan, Wen-Harn |
author_sort | Chung, Chia-Min |
collection | PubMed |
description | Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(–16) to <10(–33)). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. |
format | Online Article Text |
id | pubmed-3587614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35876142013-03-06 Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity Chung, Chia-Min Wang, Ruey-Yun Fann, Cathy S. J. Chen, Jaw-Wen Jong, Yuh-Shiun Jou, Yuh-Shan Yang, Hsin-Chou Kang, Chih-Sen Chen, Chien-Chung Chang, Huan-Cheng Pan, Wen-Harn PLoS One Research Article Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10(–16) to <10(–33)). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. Public Library of Science 2013-03-04 /pmc/articles/PMC3587614/ /pubmed/23469169 http://dx.doi.org/10.1371/journal.pone.0056119 Text en © 2013 Chung et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chung, Chia-Min Wang, Ruey-Yun Fann, Cathy S. J. Chen, Jaw-Wen Jong, Yuh-Shiun Jou, Yuh-Shan Yang, Hsin-Chou Kang, Chih-Sen Chen, Chien-Chung Chang, Huan-Cheng Pan, Wen-Harn Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title | Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title_full | Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title_fullStr | Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title_full_unstemmed | Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title_short | Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity |
title_sort | fine-mapping angiotensin-converting enzyme gene: separate qtls identified for hypertension and for ace activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587614/ https://www.ncbi.nlm.nih.gov/pubmed/23469169 http://dx.doi.org/10.1371/journal.pone.0056119 |
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