Cited by 154Coagulation, Bradykinin, Polyphosphates, and AngioedemaRenin-Angiotensin System StudiesGenetic Associations and Epidemiology

The DOI matches its Crossref record; 76 of the 77 references it cites were found in a registry or an index; 7 of the 24 sources its claims cite were checked for support.

A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P and increased risk of ACE inhibitor‐induced angioedema

Open access

Cilia La Corte, Amy L., Carter, Angela M., Rice, Gillian I., Duan, Qing Ling, Rouleau, Guy A, Adam, Albert, Grant, Peter J., Hooper, Nigel M.·2011·Human Mutation

DOI 10.1002/humu.21579

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Abstract

In a case control study of subjects with a history of ACEi-angioedema, haplotype ATG was significantly associated with ACEi-angioedema (OR 4.87 [1.78–13.35] p = 0.002). The ATG haplotype is functional and contributes to ACEi-angioedema through a reduction in APP.

Integrity signals

Registry

Crossref · 10.1002/humu.21579

Cites

76 of 76 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 24 cited sources checked · 3 supported · 1 flagged · accuracy not yet measured

The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we have shown in a well established and large family study representative of a healthy population, the Leeds Family Study [Freeman et al., 2002a[Freeman et al., , 2002b]], that genetic factors contribute to 47.3% of variation in plasma APP activity.”
- Also stated in: § Discussion · boosted
  “the results of the present study reveal a major contribution of additive genetic factors in determining variance in plasma APP activity in healthy individuals.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Partly supported
  The Abstract and Subject Recruitment sections describe a genetic study of healthy families recruited in Leeds, supporting the population and general genetic-contribution claim. But the Abstract assigns approximately 47% heritability to the FXIII complex, not plasma APP activity; the paper does not report the claimed 47.3% figure for APP activity. Page numbers were not available in our copy. (LLM, conf=0.88)
  cites Freeman et al., 2002a sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites Freeman et al., 2002b source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with the ATG haplotype associated with decreased plasma APP activity.”
- Also stated in: § Discussion · plain
  “| ATG | 41 | 0.11 (0.09-0.13) |”
- Also stated in: § Discussion · plain
  “| CGG | 235 | 0.21 (0.19-0.22) * |”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In hypertensive patients who experienced ACEi-angioedema, impaired degradation of bradykinin and des-Arg 9 -bradykinin has been associated with a decreased activity of plasma APP [Adam et al., 2002;Blais et al., 1999;Molinaro et al., 2006].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Introduction
What the sources say
- Not checked — no full text of the sourcecites Adam et al., 2002 source
- Not checked — no full text of the sourcecites Blais et al., 1999 source
- Not checked — no full text of the sourcecites Molinaro et al., 2006 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“As plasma APP is likely derived from the membranebound isoform [Hooper et al., 1990;Hooper and Turner, 1989]”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Not checked — no full text of the sourcecites Hooper et al., 1990 source
- Not checked — no full text of the sourcecites Hooper and Turner, 1989 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“In vivo it is the membrane-bound isoform of APP that metabolizes bradykinin and des-Arg 9 -bradykinin [Simmons, 2004].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Introduction
What the sources say
- Not checked — no full text of the sourcecites Simmons, 2004 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting these regions may be important for transcriptional regulation of XNPEP2 expression in vivo.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Reporter gene activity in HepG2 cells reflects XPNPEP2 promoter activity in vivo.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the ATG haplotype is modestly more informative for predicting ACEi-angioedema than the c.-2399C>A polymorphism alone.”
- Also stated in: § Discussion · plain
  “in ROC curve analysis was modestly more informative in discriminating between patients with ACEi-angioedema and controls compared with the c.-2399C>A polymorphism alone”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > ACEi-Angioedema Patients Are More Likely to Possess the ATG Haplotype Compared to Control Subjects
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes

It may state two separate claims as one. 28
Probably not a substantial claim. 14
The quote only partly states this claim. 1

At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“ACE accounts for approximately 70% of the circulatory degradation of bradykinin, with aminopeptidase P (APP; MIM# 300145) contributing to approximately 30%”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Introduction
What the sources say
- Disputed
  The Results (p. 4) report that ACE accounts for 88 ± 6% of bradykinin metabolism in the serum of 116 healthy individuals, not approximately 70%. The Results (p. 5) assign 11 ± 5% to kininase I; the paper does not assign approximately 30% to APP. (LLM, conf=0.91)
  Checked by a reasoning model — may be wrong.
  cites Cyr et al., 2001 sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites Ersahin and Simmons, 1997 source
- Not checked — no full text of the sourcecites Prechel et al., 1995 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Thus, APP inactivates bradykinin and des-Arg 9 -bradykinin [Turner and Cottrell, 2004], a role that is of major importance in the presence of ACEi [Cyr et al., 2001;Fryer et al., 2008;Kim et al., 2000].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Introduction
What the sources say
- Not checked — no full text of the sourcecites Turner and Cottrell, 2004 source
- Supported
  The Results (p. 6) report significant inverse correlations between APP activity and the half-lives of both bradykinin and des-Arg9-bradykinin in the presence of the ACE inhibitor enalaprilat. The paper also identifies APP as a pathway for metabolizing both peptides (p. 2), supporting the attributed importance of that role during ACE inhibition. (LLM, conf=0.88)
  cites Cyr et al., 2001 source
- Supported
  The Fryer et al. citation is attached to APP’s importance during ACE inhibition, not to the preceding statement about both substrates. The Discussion reports that, in rats with ACE inhibited, non-ACE breakdown of bradykinin is carried out predominantly by APP. (LLM, conf=0.93)
  cites Fryer et al., 2008 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A soluble form of APP is present in blood plasma, which has the same properties as the membrane-bound isoform [Ryan et al., 1992] and likely arises from cleavage of its glycosyl-phosphatidylinositol membrane anchor by phospholipases [Hooper et al., 1990;Hooper and Turner, 1989].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Introduction
What the sources say
- Partly supported
  The Introduction (page unavailable) identifies guinea pig serum as a source of soluble aminoacylproline hydrolase. The Comment (page unavailable) says the serum and pig kidney enzymes appear to share some properties, but explicitly says their relationship is unclear; it does not establish that they have the same properties. The phospholipase-origin clause is attributed to other citations in the citing sentence, not to Ryan et al. (LLM, conf=0.88)
  cites Ryan et al., 1992 sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites Hooper et al., 1990 source
- Not checked — no full text of the sourcecites Hooper and Turner, 1989 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“this study also identified a QTL with peak LOD = 3.75 in the vicinity of the gene encoding APP (XPNPEP2) [Duan et al., 2005].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Supported
  The Discussion (p. 8) explicitly reports a QTL near XPNPEP2 with a LOD score of 3.75. The Introduction (p. 2) identifies XPNPEP2 as the gene encoding membrane-bound APP. (LLM, conf=0.94)
  cites Duan et al., 2005 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This is similar to the estimated heritability of plasma APP of 37.5 ± 26.5% from a smaller study of eight pedigrees selected on the basis of one family member with ACEi-angioedema and/or other anaphylactoid responses to ACEi”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Partly supported
  The Variance-Component Linkage Analysis (p. 6) reports 37.5 ± 26.5% heritability for five pedigrees, not eight; its estimate for all eight is 33.6 ± 25.1%. The Participants section (p. 2) supports the description of how the eight families were selected. (LLM, conf=0.94)
  cites Duan et al., 2005 sourceExperimental — accuracy not yet measured
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The first in the region of -388 bp to -147 bp upstream of the ATG contained the proximal promoter in addition to 117 bp of the 5 UTR as defined by [Venema et al., 1997].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Not checked — no full text of the sourcecites Venema et al., 1997 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Angiotensin I-converting enzyme inhibitors (ACEi) are widely used antihypertensive agents that are associated with a potentially life-threatening reaction, ACEi-angioedema.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Abstract
What the sources say
- Not checked — no full text of the sourcecites Brown et al., 1996 source
- Not checked — no full text of the sourcecites Leenen et al., 2006 source
- Not checked — no full text of the sourcecites Vleeming et al., 1998 source
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, we have demonstrated for the first time that the c.-2399C>A polymorphism and the ATG haplotype are functional and significantly reduce transactivation of the XPNPEP2 promoter, potentially through a mechanism involving differential HNF4 binding.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Reporter gene activity in HepG2 cells reflects XPNPEP2 promoter activity in vivo.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“therefore demonstrating for the first time that c.-2399C>A and c.-1612G>T are functional polymorphisms.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Reporter gene activity in HepG2 cells reflects XPNPEP2 promoter activity in vivo.
In the paper
“HNF4 is a zinc finger protein expressed in the liver, kidney, and intestine, which is known to participate in the regulation of several genes involved in glucose, cholesterol, and fatty acid metabolism and also in the synthesis of blood coagulation factors [Schrem et al., 2002].”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
What the sources say
- Not checked — no full text of the sourcecites Schrem et al., 2002 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, we have identified and characterized a functional haplotype in the XPNPEP2 5 regulatory region that is associated with reduced plasma APP activity and increased risk for ACEi-angioedema.”
§ A Functional XPNPEP2 Promoter Haplotype Leads to Reduced Plasma Aminopeptidase P and Increased Risk of ACE Inhibitor-Induced Angioedema > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Reporter gene activity in HepG2 cells reflects XPNPEP2 promoter activity in vivo.

37 of 37

The paper relies on this without support.
The HepG2 cell line is a valid model for XPNPEP2 transcriptional regulation in the tissues relevant to ACE inhibitor-induced angioedema.
“Constructs were transiently transfected into HepG2 cells using FuGENE6 (Roche).”
“In trans-activation experiments, HepG2 cells were cotransfected with 0.4 μg reporter construct and 0.1 μg hepatic nuclear factor-4 (HNF4) expression vector”
The paper relies on this without support.
The Angioedema Study cases and controls are representative of the broader population at risk for ACE inhibitor-induced angioedema.
“The Angioedema Study: consisted of 34 participants from Canada, Belgium, and the United States who had a history of ACEiangioedema or ACEi-induced anaphylactoid reactions and 127 control samples, matched for gender and country of origin.”
The paper relies on this without support.
The Leeds Family Study sample is representative of healthy individuals for estimating the genetic contribution to plasma APP activity.
“The Leeds Family Study: consisted of 537 subjects from 89 pedigrees (average of six subjects per family) from 133 households.”
The paper relies on this without support.
Reporter gene activity in HepG2 cells reflects XPNPEP2 promoter activity in vivo.
“suggesting these regions may be important for transcriptional regulation of XNPEP2 expression in vivo.”
“demonstrating for the first time that c.-2399C>A and c.-1612G>T are functional polymorphisms.”

4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

The minimal promoter has two reported boundaries
Minor
The results identify the minimal promoter as extending from −338 to −147 bp, but the discussion places its upstream boundary at −388 bp. Those boundaries differ by 50 bp.

1 of 1

A New Statistical Method for Haplotype Reconstruction from Population Data
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A Comparison of Bayesian Methods for Haplotype Reconstruction from Population Genotype Data
Stephens, M., & Donnelly, P. (2003) · The American Journal of Human Genetics · doi:10.1086/379378 · Cited by 3,516
Multipoint Quantitative-Trait Linkage Analysis in General Pedigrees
Almasy, L. A., & Blangero, J. (1998) · The American Journal of Human Genetics · doi:10.1086/301844 · Cited by 3,021
International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences
Leeb-Lundberg, L. M. F., Marceau, F., Müller‐Esterl, W., Pettibone, D. J., & Zuraw, B. L. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.2 · Cited by 956
Cough and Angioneurotic Edema Associated with Angiotensin-Converting Enzyme Inhibitor Therapy: A Review of the Literature and Pathophysiology
Israili, Z. H., & Hall, W. D. (1992) · Annals of Internal Medicine · doi:10.7326/0003-4819-117-3-234 · Cited by 910 · cited 1×
“The vasodilator peptide bradykinin plays a central role in the pathophysiology of ACEi-induced angioedema (ACEi-angioedema) [Israili and Hall, 1992].”
Background
Plasma bradykinin in angio-oedema
Nussberger, J., Cugno, M., Amstutz, C., Cicardi, M., Pellacani, A., & Agostoni, A. (1998) · The Lancet · doi:10.1016/s0140-6736(97)09137-x · Cited by 706
Classification, diagnosis, and approach to treatment for angioedema: consensus report from the H ereditary A ngioedema I nternational W orking G roup
Cicardi, M., Aberer, W., Banerji, A., Baş, M., Bernstein, J. A., Bork, K., Caballero, T., Farkas, H., Grumach, A. S., Kaplan, A. P., et al. (2014) · Allergy · doi:10.1111/all.12380 · Cited by 659
Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial
Kostis, J. (2004) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2003.09.014 · Cited by 579
Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor
(2006) · doi:10.1016/j.bbrc.2006.03.092 · Cited by 407
The angiotensin–converting enzyme gene family: genomics and pharmacology
Turner, A. J., & Hooper, N. M. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01994-5 · Cited by 407
Self-citation

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Show all 77 references

1 of the 77 references couldn’t be matched to a known paper.

Sorted by citations

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Neutral endopeptidase inhibition and the natriuretic peptide system: an evolving strategy in cardiovascular therapeutics
Mangiafico, S., Costello‐Boerrigter, L. C., Andersen, I. A., Cataliotti, A., & Burnett, J. C. J. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs262 · Cited by 275
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ACE Inhibitor-Induced Angioedema: a Review
Kostis, W. J., Shetty, M., Chowdhury, Y. S., & Kostis, J. B. (2018) · Current Hypertension Reports · doi:10.1007/s11906-018-0859-x · Cited by 145

See all 154

Authors: Cilia La Corte, A. L., Carter, A. M., Rice, G. I., Duan, Q. L., Rouleau, G. A., Adam, A., Grant, P. J., & Hooper, N. M.
Affiliations: University of Leeds (GB)
McGill University (CA)
Centre Hospitalier de l’Université de Montréal (CA)
Université de Montréal (CA)
Corresponding author: Hooper, Nigel M.
ORCID: Carter, Angela M.
Rice, Gillian I.
Duan, Qing Ling
Rouleau, Guy A
Adam, Albert
Grant, Peter J.
Hooper, Nigel M.
Venue: Human Mutation
Publisher: Wiley
Published: 2011-09-12
Volume: 32
Issue: 11
Pages: 1326-1331
ISSN: 1059-7794 (ISSN-L)
DOI: 10.1002/humu.21579
OpenAlex: W2038331078
Semantic Scholar: 00e2999e2998ccdf31e93b0ff6c5956f18405ae5
Cited by: 154
References: 77
Citations by year: 2026: 3 · 2025: 2 · 2024: 1 · 2023: 9 · 2021: 15 · 2020: 12 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 22 · 2015: 18 · 2014: 14 · 2013: 3 · 2012: 7
FWCI: 4.04
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1450 d)
Locations: Human Mutation (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: University of Cincinnati
CSL Behring
British Heart Foundation (PG/02/106/14434, FS/02/058/14378)
Topics: Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: aminopeptidase P, ACE inhibitor-induced angioedema, promoter haplotypes, genetic polymorphism, enhancers, bradykinin metabolism, plasma enzyme activity, genetic susceptibility
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Aminopeptidases, Angioedema, Angiotensin-Converting Enzyme Inhibitors, Female, Haplotypes, Humans, Male, Middle Aged, Pedigree, Promoter Regions, Genetic, Regulatory Elements, Transcriptional

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A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P and increased risk of ACE inhibitor‐induced angioedema

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