Background: Insect venom allergy (IVA) is present in 1–3% of the population. A group of patients with high specific IgE do not react to stings. In contrast, a proportion of patients with IVA have low specific IgE levels. These findings indicate that factors other than specific IgE may also be involved in IVA. Dysfunction of the renin-angiotensin system (RAS) has been described as a potential factor in IVA. The objective of this study was to determine the prevalence of angiotensin AGT p.M235T and angiotensin-converting enzyme ACE I/D, I/I, D/D gene polymorphisms in patients with IVA and to relate the presence of these gene variants to the course of IVA and the safety of treatment. Methods: A total of 107 patients with IVA and 113 controls were studied. AGT p.M235T and ACE (ID, I/I, D/D) gene polymorphisms were examined, and angiotensin I levels were measured by immunoassay. Results: The frequency of the AGT MM M235T variant was significantly higher in IVA patients (29.9%) than in controls (17%, p = 0.02). The presence of the MM M235T genotype increased the risk of grade IV reactions (odds ratio = 2.5 and 95% confidence interval 1.04–6.08). There were no differences in the prevalence of the ACE I/D polymorphism and angiotensin I levels between control groups and patients with different grades of anaphylactic reactions or patients with side effects of venom immunotherapy. Conclusion: The AGT M235T MM variant may be responsible for severe anaphylactic reactions to insect venom allergens in some patients.

Keywords:
Genetics, I/D ACE, Insect venom allergy, M235T AGT
1.
Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN: Diagnosis of Hymenoptera venom allergy. Allergy 2005;60:1339–1349.
2.
Bonifazi F, Jutel M, Bilo BM, Birnbaum J, Muller U: Prevention and treatment of Hymenoptera venom allergy: guidelines for clinical practice. Allergy 2005;60:1459–1470.
3.
Finegold I: Issues in stinging insect allergy immunotherapy: a review. Curr Opin Allergy Clin Immunol 2008;8:343–347.
4.
Lieberman P: Epidemiology of anaphylaxis. Curr Opin Allergy Clin Immunol 2008;8:316–320.
5.
Mueller HL: Diagnosis and treatment of insect sensitivity. J Asthma Res 1966;3:331–333.
6.
Hermann K, Ring J: The renin-angiotensin system in patients with repeated anaphylactic reactions during Hymenoptera venom hyposensitization and sting challenge. Int Arch Allergy Immunol 1997;112:251–256.
7.
Hermann K, Ring J: Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with Hymenoptera venom anaphylaxis. Int Arch Allergy Immunol 1994;104:379–384.
8.
Hermann K, Ring J: Association between the renin angiotensin system and anaphylaxis. Adv Exp Med Biol 1995;377:299–309.
9.
Hermann K, Ring J: Human leukocytes contain angiotensin I, angiotensin II and angiotensin metabolites. Int Arch Allergy Immunol 1994;103:152–159.
10.
Hermann K, Ring J: The renin angiotensin system and Hymenoptera venom anaphylaxis. Clin Exp Allergy 1993;23:762–769.
11.
Hermann K, Donhauser S, Ring J: Angiotensin in human leukocytes of patients with insect venom anaphylaxis and healthy volunteers. Int Arch Allergy Immunol 1995;107:385–386.
12.
Rush JW, Aultman CD: Vascular biology of angiotensin and the impact of physical activity. Appl Physiol Nutr Metab 2008;33:162–172.
13.
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F: An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343–1346.
14.
Azizi M, Hallouin MC, Jeunemaitre X, Guyene T, Menard J: Influence of the M235T polymorphism of human angiotensinogen (AGT) on plasma AGT and renin concentrations after ethinylestradiol administration. J Clin Endocr Metab 2000;85:4331–4337.
15.
Mondorf UF, Russ A, Wiesemann A, Herrero M, Oremek G, Lenz T: Contribution of angiotensin I converting enzyme gene polymorphism and angiotensinogen gene polymorphism to blood pressure regulation in essential hypertension. Am J Hypertens 1998;11:174–183.
16.
Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH: A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 1995;332:706–711.
17.
Prasad A, Narayanan S, Waclawiw MA, Epstein N, Quyyumi AA: The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. J Am Coll Cardiol 2000;36:1579–1586.
18.
Villard E, Tiret L, Visvikis S, Rakotovao R, Cambien F, Soubrier F: Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am J Hum Genet 1996;58:1268–1278.
19.
Benessiano J, Crestani B, Mestari F, Klouche W, Neukirch F, Hacein-Bey S, Durand G, Aubier M: High frequency of a deletion polymorphism of the angiotensin-converting enzyme gene in asthma. J Allergy Clin Immunol 1997;99:53–57.
20.
Holla L, Vask A, Znojil V, Sisková L, Vácha J: Association of 3 gene polymorphisms with atopic diseases. J Allergy Clin Immunol 1999;103:702–708.
21.
Kim JJ, Kim HJ, Lee IK, Chung HT, Lee JH: Association between polymorphisms of the angiotensin-converting enzyme and angiotensinogen genes and allergic rhinitis in a Korean population. Ann Otol Rhinol Laryngol 2004;113:297–302.
22.
Lee YC, Cheon KT, Lee HB, Kim W, Rhee YK, Kim DS: Gene polymorphism of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma. Allergy 2000;55:959–963.
23.
Kim TH, Chang HS, Park SM, Nam BY, Park JS, Rhim T, Park HS, Kim MK, Choi IS, Cho SH, Chung IY, Park BL, Park CS, Shin HD: Association of angiotensin I-converting enzyme gene polymorphisms with aspirin intolerance in asthmatics. Clin Exp Allergy 2008;38:1727–1737.
24.
Brasier AR, Ron D, Tate JE, Habener JF: A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced, NF kappa B mediated trans-activation of the angiotensinogen gene acute-phase response element. EMBO J 1990;9:3933–3944.
25.
Stumpf JL, Shehab N, Patel AC: Safety of angiotensin-converting enzyme inhibitors in patients with insect venom allergies. Ann Pharmacother 2006;40:699–703.
26.
White KM, England RW: Safety of angiotensin-converting enzyme inhibitors while receiving venom immunotherapy. Ann Allergy Asthma Immunol 2008;101:426–430.
27.
Lieberman P: Anaphylaxis. Med Clin North Am 2006;90:77–95.
28.
Jutel M, Akdis M, Blaser K, Akdis CA: Mechanisms of allergen specific immunotherapy – T-cell tolerance and more. Allergy 2006;61:796–807.
29.
Kawabata Y, Yang TS, Yokochi TT, Matsushita M, Fujita T, Shibazaki M, Noikura T, Endo TY, Takada H: Complement system is involved in anaphylactoid reaction induced by lipopolysaccharides in muramyldipeptide-treated mice. Shock 2000;14:572–577.
30.
Volcheck G, Butterfield J, Yunginger J, Klee G: Elevated serum levels of calcitonin gene-related peptide in Hymenoptera venom anaphylaxis. J Allergy Clin Immunol 1998;102:149–151.
31.
Konno S, Hizawa N, Nishimura M, Huang SK: Osteopontin: a potential biomarker for successful bee venom immunotherapy and a potential molecule for inhibiting IgE-mediated allergic responses. Allergol Int 2006;55:355–359.
32.
Lawley H, Hird H, Mallinder P: Detection of an activating c-kit mutation by real-time PCR in patients with anaphylaxis. Mutat Res 2005;572:1–13.
© 2010 S. Karger AG, Basel
2010
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.