World Journal of Pediatrics

, Volume 13, Issue 1, pp 34–40 | Cite as

Endothelial nitric oxide synthase gene polymorphisms are associated with sensitization to seasonal aeroallergens in asthmatic children

  • Maria Iordanidou
  • Emmanouil Paraskakis
  • Anna Tavridou
  • Athanasios Chatzimichael
  • Vangelis G. Manolopoulos
Original article

Abstract

Background

Childhood asthma phenotype is the consequence of interaction between environment and genetic factors. Nitric oxide (NO) formation is affected by polymorphisms in nitric oxide synthase (NOS) enzymes, which play a significant role as inflammatory factors in the airways. This study was undertaken to estimate the correlation of -786C>T and 894G>T polymorphisms of the eNOS gene with the sensitization of asthmatic children to common aeroallergens.

Methods

A total of 193 asthmatic children and 96 healthy controls, who were of Mediterranean origin, living in the same geographical area, were enrolled in the study. 894G>T and -786T/C polymorphisms of the eNOS gene were analyzed using a PCR-RFLP method.

Results

The 894GG genotype was more frequent (68.6%) in children with asthma sensitized to Oleaeuropaea than in those with asthma non-sensitized (43.0%) (P=0.004). Likewise, -786TT genotype frequency was higher in children with asthma sensitized to Oleaeuropaea (51.0%) than in those with asthma nonsensitized (31.7%) to this allergen (P=0.035). For the aeroallergens Parietariajudaica and mixed grass, the frequency of -786C allele carriage was associated with protection from sensitization to Parietariajudaica and mixed grass in asthmatic children (P=0.021 and P=0.017, respectively). In the healthy control group, the genotype frequencies for these polymorphisms were similar to genotype frequencies of children with asthma non-sensitized to these three specific aeroallergens.

Conclusion

In children with asthma, 894G>T and -786T/C polymorphisms of the eNOS gene were correlated with sensitization to common seasonal aeroallergens.

Key words

asthma atopy genetics nitric oxide 

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References

  1. 1.
    Sengler C, Lau S, Wahn U, Nickel R. Interactions between genes and environmental factors in asthma and atopy: new developments. Respir Res 2002;3:7.CrossRefPubMedGoogle Scholar
  2. 2.
    Batra J, Das S, Chatterjee R, Chandra S, Ghosh B. Monocyte chemotactic protein (MCP3) promoter polymorphism is associated with atopic asthma in the Indian population. J Allergy Clin Immunol 2011;128:239–242. e3.CrossRefPubMedGoogle Scholar
  3. 3.
    Murk W, Walsh K, Hsu LI, Zhao L, Bracken MB, Dewan AT. Attempted replication of 50 reported asthma risk genes identifies a SNP in RAD50 as associated with childhood atopic asthma. Hum Hered 2011;71:97–105.CrossRefPubMedGoogle Scholar
  4. 4.
    Bove P F, van der Vliet A. Nitric oxide and reactive nitrogen species in airway epithelial signaling and inflammation. Free Radic Biol Med 2006;41:515–527.CrossRefPubMedGoogle Scholar
  5. 5.
    Baraldi E, de Jongste JC, European Respiratory Society/American Thoracic Society (ERS/ATS) Task Force. Measurement of exhaled nitric oxide in children, 2001. Eur Respir J 2002;20:223–237.CrossRefPubMedGoogle Scholar
  6. 6.
    Barnes PJ. NO or no NO in asthma? Thorax 1996;51:218–220.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Sippe JM, Holden WE, Tilles SA, O’Hollaren M, Cook J, Thukkani N, et al. Exhaled nitric oxide levels correlate with measures of disease control in asthma. J Allergy Clin Immunol 2000;106:645–650.CrossRefGoogle Scholar
  8. 8.
    Lehtimaki L, Kankaanranta H, Saarelainen S, Hahtola P, Jarvenpaa R, Koivula T, et al. Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation. Am J Respir Crit Care Med 2001;163:1557–1561.CrossRefPubMedGoogle Scholar
  9. 9.
    Paraskakis E, Brindicci C, Fleming L, Krol R, Kharitonov SA, Wilson NM, et al. Measurement of bronchial and alveolar nitric oxide production in normal children and children with asthma. Am J Respir Crit Care Med 2006;174:260–267.CrossRefPubMedGoogle Scholar
  10. 10.
    Berlyne GS, Parameswaran K, Kamada D, Efthimiadis A, Hargreave FE. A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation. J Allergy Clin Immunol 2000;106:638–644.CrossRefPubMedGoogle Scholar
  11. 11.
    Gratziou C, Lignos M, Dassiou M, Roussos C. Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis. Eur Respir J 1999;14:897–901.CrossRefPubMedGoogle Scholar
  12. 12.
    Charles IG, Scorer CA, Moro MA, Fernandez C, Chubb A, Dawson J, et al. Expression of human nitric oxide synthase isozymes. Methods Enzy mol 1996;268:449–460.CrossRefGoogle Scholar
  13. 13.
    Tulic MK, Wale JL, Holt PG, Sly PD. Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model. Eur Respir J 2000;15:870–877.CrossRefPubMedGoogle Scholar
  14. 14.
    Lee YC, Cheon KT, Lee HB, Kim W, Rhee YK, Kim DS. Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma. Allergy 2000;55:959–963.CrossRefPubMedGoogle Scholar
  15. 15.
    Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 1993;268:17478–17488.PubMedGoogle Scholar
  16. 16.
    Holla LI, Buckova D, Kuhrova V, Stejskalova A, Francova H, Znojil V, et al. Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma. Clin Exp Allergy 2002;32:1193–1198.CrossRefPubMedGoogle Scholar
  17. 17.
    Miyamoto Y, Saito Y, Nakayama M, Shimasaki Y, Yoshimura T, Yoshimura M, et al. Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a-786T—>C mutation associated with coronary spastic angina. Hum Mol Genet 2000;9:2629–2637.CrossRefPubMedGoogle Scholar
  18. 18.
    Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J. Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci U S A 2000;97:2832–2835.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Leung TF, Liu EK, Tang NL, Ko FW, Li CY, Lam CW, et al. Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children. Clin Exp Allergy 2005;35:1288–1294.CrossRefPubMedGoogle Scholar
  20. 20.
    Salam MT, Bastain TM, Rappaport EB, Islam T, Berhane K, Gauderman WJ, et al. Genetic variations in nitric oxide synthase and arginase influence exhaled nitric oxide levels in children. Allergy 2011;66:412–419.CrossRefPubMedGoogle Scholar
  21. 21.
    Gelfand E W. Pediatric asthma: a different disease. Proc Am Thorac Soc 2009;6:278–282.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Ragia G, Nikolaidis E, Tavridou A, Arvanitidis KI, Kanoni S, Dedoussis GV, et al. Endothelial nitric oxide synthase gene polymorphisms-786T > C and 894G > T in coronary artery bypass graft surgery patients. Hum Genomics 2010;4:375–383.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ohtoshi K, Yamasaki Y, Gorogawa S, Hayaishi-Okano R, Node K, Matsuhisa M, et al. Association of (-)786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance. Diabetologia 2002;45:1594–1601.CrossRefPubMedGoogle Scholar
  24. 24.
    Arshad SH, Karmaus W, Matthews S, Mealy B, Dean T, Frischer T, et al. Association of allergy-related symptoms with sensitisation to common allergens in an adult European population. J Investig Allergol Clin Immunol 2001;11:94–102.PubMedGoogle Scholar
  25. 25.
    Kaleyias J, Papaioannou D, Manoussakis M, Syrigou E, Tapratzi P, Saxoni-Papageorgiou P. Skin-prick test findings in atopic asthmatic children: a follow-up study from childhood to puberty. Pediatr Allergy Immunol 2002;13:368–374.CrossRefPubMedGoogle Scholar
  26. 26.
    Wambre E, Bonvalet M, Bodo VB, Maillère B, Leclert G, Moussu H, et al. Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4(+) T cell responses. Clin Exp Allergy 2011;41:192–203.CrossRefPubMedGoogle Scholar
  27. 27.
    Holla LI, Jurajda M, Pohunek P, Znojil V. Haplotype analysis of the endothelial nitric oxide synthase gene in asthma. Hum Immunol 2008;69:306–313.CrossRefPubMedGoogle Scholar
  28. 28.
    Storm van’s Gravesande K, Wechsler ME, Grasemann H, Silverman ES, Le L, Palmer LJ, et al. Association of a missense mutation in the NOS3 gene with exhaled nitric oxide levels. Am J Respir Crit Care Med 2003;168:228–231.CrossRefPubMedGoogle Scholar
  29. 29.
    Gao PS, Kawada H, Kasamatsu T, Mao XQ, Roberts MH, Miyamoto Y, et al. Variants of NOS1, NOS2, and NOS3 genes in asthmatics. Biochem Biophys Res Commun 2000;267:761–763.CrossRefPubMedGoogle Scholar
  30. 30.
    Djidjik R, Ghaffor M, Brun M, Gharnaout M, Salah SS, Boukouaci W, et al. Constitutive nitric oxide synthase gene polymorphisms and house dust mite respiratory allergy in an Algerian patient group. Tissue Antigens 2008;71:160–164.CrossRefPubMedGoogle Scholar
  31. 31.
    Holla LI, Stejskalova A, Znojil V, Vasku A. Association study of promoter polymorphisms within the NOS3 gene and allergic diseases. Int Arch Allergy Immunol 2006;141:103–109.CrossRefPubMedGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Maria Iordanidou
    • 1
  • Emmanouil Paraskakis
    • 1
    • 3
  • Anna Tavridou
    • 2
  • Athanasios Chatzimichael
    • 1
  • Vangelis G. Manolopoulos
    • 2
  1. 1.Respiratory Unit, Department of PediatricsUniversity Hospital of AlexandroupolisAlexandroupolis, ThraceGreece
  2. 2.Laboratory of Pharmacology, Medical SchoolDemocritus University of ThraceAlexandroupolisGreece
  3. 3.Respiratory Unit, Department of PediatricsAcademic General Hospital of AlexandroupolisDragana Alexandroupolis, ThraceGreece

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