A genome-wide association study identifies new loci for ACE activity: Potential implications for response to ACE inhibitor

C. M. Chung; R. Y. Wang; J. W. Chen; C. S.J. Fann; H. B. Leu; H. Y. Ho; C. T. Ting; T. H. Lin; S. H. Sheu; W. C. Tsai; J. H. Chen; Y. S. Jong; S. J. Lin; Y. T. Chen; W. H. Pan

doi:10.1038/tpj.2009.70

A genome-wide association study identifies new loci for ACE activity: Potential implications for response to ACE inhibitor

C. M. Chung, R. Y. Wang, J. W. Chen, C. S.J. Fann, H. B. Leu, H. Y. Ho, C. T. Ting, T. H. Lin, S. H. Sheu, W. C. Tsai, J. H. Chen, Y. S. Jong, S. J. Lin, Y. T. Chen, W. H. Pan

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

104 Citations (Scopus)

Abstract

Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 × 10^-25), rs495828 (P=3.5 × 10^-8) and rs8176746 (P=9.3 × 10^-5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.

Original language	English
Pages (from-to)	537-544
Number of pages	8
Journal	Pharmacogenomics Journal
Volume	10
Issue number	6
DOIs	https://doi.org/10.1038/tpj.2009.70
Publication status	Published - 2010 Dec

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Pharmacology

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Chung, C. M., Wang, R. Y., Chen, J. W., Fann, C. S. J., Leu, H. B., Ho, H. Y., Ting, C. T., Lin, T. H., Sheu, S. H., Tsai, W. C., Chen, J. H., Jong, Y. S., Lin, S. J., Chen, Y. T., & Pan, W. H. (2010). A genome-wide association study identifies new loci for ACE activity: Potential implications for response to ACE inhibitor. Pharmacogenomics Journal, 10(6), 537-544. https://doi.org/10.1038/tpj.2009.70

@article{985b1b565a65474eab9125a58b162c01,

title = "A genome-wide association study identifies new loci for ACE activity: Potential implications for response to ACE inhibitor",

abstract = "Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 × 10-25), rs495828 (P=3.5 × 10-8) and rs8176746 (P=9.3 × 10-5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.",

author = "Chung, {C. M.} and Wang, {R. Y.} and Chen, {J. W.} and Fann, {C. S.J.} and Leu, {H. B.} and Ho, {H. Y.} and Ting, {C. T.} and Lin, {T. H.} and Sheu, {S. H.} and Tsai, {W. C.} and Chen, {J. H.} and Jong, {Y. S.} and Lin, {S. J.} and Chen, {Y. T.} and Pan, {W. H.}",

note = "Funding Information: We thank John Yin for editing the paper and Academia Sinica National Genotyping Center (Taipei, Taiwan) for performing genotyping of the second-stage subjects. This research was supported by the Department of Health (DOH90-TD-1037), the National Science Council (NSC91-3112-P-001-025-YGPCP91-25), Academia Sinica (AS91IBMS2PP-A) and Academia Sinica Genomics and Proteinomics Program (2003–2006) in Taiwan.",

year = "2010",

month = dec,

doi = "10.1038/tpj.2009.70",

language = "English",

volume = "10",

pages = "537--544",

journal = "Pharmacogenomics Journal",

issn = "1470-269X",

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TY - JOUR

T1 - A genome-wide association study identifies new loci for ACE activity

T2 - Potential implications for response to ACE inhibitor

AU - Chung, C. M.

AU - Wang, R. Y.

AU - Chen, J. W.

AU - Fann, C. S.J.

AU - Leu, H. B.

AU - Ho, H. Y.

AU - Ting, C. T.

AU - Lin, T. H.

AU - Sheu, S. H.

AU - Tsai, W. C.

AU - Chen, J. H.

AU - Jong, Y. S.

AU - Lin, S. J.

AU - Chen, Y. T.

AU - Pan, W. H.

N1 - Funding Information: We thank John Yin for editing the paper and Academia Sinica National Genotyping Center (Taipei, Taiwan) for performing genotyping of the second-stage subjects. This research was supported by the Department of Health (DOH90-TD-1037), the National Science Council (NSC91-3112-P-001-025-YGPCP91-25), Academia Sinica (AS91IBMS2PP-A) and Academia Sinica Genomics and Proteinomics Program (2003–2006) in Taiwan.

PY - 2010/12

Y1 - 2010/12

N2 - Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 × 10-25), rs495828 (P=3.5 × 10-8) and rs8176746 (P=9.3 × 10-5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.

AB - Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 × 10-25), rs495828 (P=3.5 × 10-8) and rs8176746 (P=9.3 × 10-5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.

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DO - 10.1038/tpj.2009.70

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JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 6

ER -

A genome-wide association study identifies new loci for ACE activity: Potential implications for response to ACE inhibitor

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