Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

Seyed H. Mahmoudpour, Abirami Veluchamy, Moneeza K. Siddiqui, Folkert W. Asselbergs, Patrick C. Souverein, Catherine E. de Keyser, Albert Hofman, Chim C. Lang, Alexander S. F. Doney, Bruno H. Stricker, Anthonius de Boer, Anke-Hilse Maitland-van der Zee (Lead / Corresponding author), Colin N. A. Palmer (Lead / Corresponding author), on behalf of the PREDICTION-ADR consortium

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Abstract

OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker.

METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.

RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95% confidence interval: 1.32-1.76), P=6.2×10].

CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.

Original languageEnglish
Pages (from-to)112-119
Number of pages8
JournalPharmacogenetics and Genomics
Volume27
Issue number3
Early online date26 Dec 2016
DOIs
Publication statusPublished - Mar 2017

Fingerprint

Genome-Wide Association Study
Angiotensin-Converting Enzyme Inhibitors
Meta-Analysis
RNA-Binding Proteins
Single Nucleotide Polymorphism
Angiotensin Receptor Antagonists
Caenorhabditis elegans
Scotland
Aminobutyrates
Acyltransferases
Gene Frequency
Sarcoma
Netherlands
Introns
Genes
Membrane Proteins
Software
Odds Ratio
Confidence Intervals
Research

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Angiotensin-converting enzyme-inhibitor intolerance
  • Adverse drug reaction
  • Angio-oedema
  • cough
  • genome-wide association study

Cite this

Mahmoudpour, S. H., Veluchamy, A., Siddiqui, M. K., Asselbergs, F. W., Souverein, P. C., de Keyser, C. E., ... on behalf of the PREDICTION-ADR consortium (2017). Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors. Pharmacogenetics and Genomics, 27(3), 112-119. https://doi.org/10.1097/FPC.0000000000000264
Mahmoudpour, Seyed H. ; Veluchamy, Abirami ; Siddiqui, Moneeza K. ; Asselbergs, Folkert W. ; Souverein, Patrick C. ; de Keyser, Catherine E. ; Hofman, Albert ; Lang, Chim C. ; Doney, Alexander S. F. ; Stricker, Bruno H. ; de Boer, Anthonius ; Maitland-van der Zee, Anke-Hilse ; Palmer, Colin N. A. ; on behalf of the PREDICTION-ADR consortium. / Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors. In: Pharmacogenetics and Genomics. 2017 ; Vol. 27, No. 3. pp. 112-119.
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abstract = "OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker.METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95{\%} confidence interval: 1.32-1.76), P=6.2×10].CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.",
keywords = "Angiotensin-converting enzyme inhibitors , Angiotensin-converting enzyme-inhibitor intolerance , Adverse drug reaction, Angio-oedema, cough, genome-wide association study",
author = "Mahmoudpour, {Seyed H.} and Abirami Veluchamy and Siddiqui, {Moneeza K.} and Asselbergs, {Folkert W.} and Souverein, {Patrick C.} and {de Keyser}, {Catherine E.} and Albert Hofman and Lang, {Chim C.} and Doney, {Alexander S. F.} and Stricker, {Bruno H.} and {de Boer}, Anthonius and {Maitland-van der Zee}, Anke-Hilse and Palmer, {Colin N. A.} and {on behalf of the PREDICTION-ADR consortium}",
note = "This research was conducted as a part of the Personalisation of treatment In Cardiovascular disease through next generation sequencing in Adverse Drug Reactions (PREDICTION-ADR) consortium. The PREDICTION-ADR project is supported by the European Union FP7 Grant no. 602108.",
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language = "English",
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pages = "112--119",
journal = "Pharmacogenetics and Genomics",
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Mahmoudpour, SH, Veluchamy, A, Siddiqui, MK, Asselbergs, FW, Souverein, PC, de Keyser, CE, Hofman, A, Lang, CC, Doney, ASF, Stricker, BH, de Boer, A, Maitland-van der Zee, A-H, Palmer, CNA & on behalf of the PREDICTION-ADR consortium 2017, 'Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors', Pharmacogenetics and Genomics, vol. 27, no. 3, pp. 112-119. https://doi.org/10.1097/FPC.0000000000000264

Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors. / Mahmoudpour, Seyed H.; Veluchamy, Abirami; Siddiqui, Moneeza K.; Asselbergs, Folkert W.; Souverein, Patrick C.; de Keyser, Catherine E.; Hofman, Albert; Lang, Chim C.; Doney, Alexander S. F.; Stricker, Bruno H.; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse (Lead / Corresponding author); Palmer, Colin N. A. (Lead / Corresponding author); on behalf of the PREDICTION-ADR consortium.

In: Pharmacogenetics and Genomics, Vol. 27, No. 3, 03.2017, p. 112-119.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Meta-analysis of genome-wide association studies on the intolerance of angiotensin-converting enzyme inhibitors

AU - Mahmoudpour, Seyed H.

AU - Veluchamy, Abirami

AU - Siddiqui, Moneeza K.

AU - Asselbergs, Folkert W.

AU - Souverein, Patrick C.

AU - de Keyser, Catherine E.

AU - Hofman, Albert

AU - Lang, Chim C.

AU - Doney, Alexander S. F.

AU - Stricker, Bruno H.

AU - de Boer, Anthonius

AU - Maitland-van der Zee, Anke-Hilse

AU - Palmer, Colin N. A.

AU - on behalf of the PREDICTION-ADR consortium

N1 - This research was conducted as a part of the Personalisation of treatment In Cardiovascular disease through next generation sequencing in Adverse Drug Reactions (PREDICTION-ADR) consortium. The PREDICTION-ADR project is supported by the European Union FP7 Grant no. 602108.

PY - 2017/3

Y1 - 2017/3

N2 - OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker.METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95% confidence interval: 1.32-1.76), P=6.2×10].CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.

AB - OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker.METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch. Genome-wide association study (GWAS) using an additive model was run in these sets and the results were meta-analysed using Genome-Wide Association Meta Analysis software.RESULTS: A total of 972 cases out of 5161 ACE-inhibitor starters were identified. Eight SNPs within four genes reached the genome-wide association study significance level (P<5×10) in the meta-analysis [RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), γ-aminobutyric acid receptor subunit γ-2, sarcoma (Src) homology 2 (SH2) B adaptor protein 1 and membrane bound O-acyltransferase domain containing 1]. The strongest associated SNP was located in an intron of RNA binding protein, Fox-1 homolog (Caenorhabditis elegans), which contains an RNA binding protein [rs2061538: minor allele frequency=0.16, odds ratio=1.52 (95% confidence interval: 1.32-1.76), P=6.2×10].CONCLUSION: These results indicate that genetic variation in the above-mentioned genes may increase the risk of ACE-inhibitor-induced adverse reactions.

KW - Angiotensin-converting enzyme inhibitors

KW - Angiotensin-converting enzyme-inhibitor intolerance

KW - Adverse drug reaction

KW - Angio-oedema

KW - cough

KW - genome-wide association study

U2 - 10.1097/FPC.0000000000000264

DO - 10.1097/FPC.0000000000000264

M3 - Article

VL - 27

SP - 112

EP - 119

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 3

ER -