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

Publication ,  Journal Article
Chung, C-M; Wang, R-Y; Chen, J-W; Fann, CSJ; 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 ...
Published in: Pharmacogenomics J
December 2010

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 x 10⁻²⁵), rs495828 (P=3.5 x 10⁻⁸) and rs8176746 (P=9.3 x 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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Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

537 / 544

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Peptidyl-Dipeptidase A
  • Male
  • Hypertension
  • Humans
  • Genome-Wide Association Study
  • Female
  • Blood Pressure
 

Citation

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Chung, C.-M., Wang, R.-Y., Chen, J.-W., Fann, C. S. J., Leu, H.-B., Ho, H.-Y., … Pan, W.-H. (2010). A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. Pharmacogenomics J, 10(6), 537–544. https://doi.org/10.1038/tpj.2009.70
Chung, C. -. M., R. -. Y. Wang, J. -. W. Chen, C. S. J. Fann, H. -. B. Leu, H. -. Y. Ho, C. -. T. Ting, et al. “A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor.Pharmacogenomics J 10, no. 6 (December 2010): 537–44. https://doi.org/10.1038/tpj.2009.70.
Chung C-M, Wang R-Y, Chen J-W, Fann CSJ, Leu H-B, Ho H-Y, et al. A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. Pharmacogenomics J. 2010 Dec;10(6):537–44.
Chung, C. .. M., et al. “A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor.Pharmacogenomics J, vol. 10, no. 6, Dec. 2010, pp. 537–44. Pubmed, doi:10.1038/tpj.2009.70.
Chung C-M, Wang R-Y, Chen J-W, Fann CSJ, 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. A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. Pharmacogenomics J. 2010 Dec;10(6):537–544.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

December 2010

Volume

10

Issue

6

Start / End Page

537 / 544

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Peptidyl-Dipeptidase A
  • Male
  • Hypertension
  • Humans
  • Genome-Wide Association Study
  • Female
  • Blood Pressure