Skip to main content

Advertisement

Log in

RANTES Gene Promoter Polymorphisms Are Associated with Bronchial Hyperresponsiveness in Korean Children with Asthma

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Regulated upon activation in normal T cells, expressed, and secreted (RANTES) protein is abundantly expressed during atopic asthma, suggesting that it is an important mediator of this disease. The aim of this study was to evaluate the possible role of RANTES promoter polymorphisms in children with asthma. We genotyped 271 children with atopic asthma, 55 children with nonatopic asthma, and 253 control children for allelic determinants at two polymorphic sites in the promoter region at positions −403G>A and −28C>G by restriction fragment length polymorphism methods. There was no significant difference in genotype and allele frequencies of the RANTES −403G>A and −28C>G polymorphisms when the atopic asthma, nonatopic asthma, and control groups were compared. However, atopic asthmatic patients who were homozygous GG for the RANTES −28C>G tended to have lower PC20 methacholine than those carrying the wild genotype. In addition, a significantly lower PC20 was demonstrated for the homozygous haplotype −403A/−28G in asthmatic children. The polymorphisms within the RANTES promoter may have a disease-modifying effect in Korean children with asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Maddox L, Schwartz DA (2002) The pathophysiology of asthma. Annu Rev Med 53:477–498

    Article  PubMed  CAS  Google Scholar 

  2. Sengler C, Lau S, Wahn U, Nickel R (2002) Interactions between genes and environmental factors in asthma and atopy: new developments. Respir Res 3:7

    Article  PubMed  Google Scholar 

  3. Alam R (1997) Chemokines in allergic inflammation. J Allergy Clin Immunol 99:273–277

    Article  PubMed  CAS  Google Scholar 

  4. Schall TJ, Bacon K, Toy KJ, Goeddel DV (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669–671

    Article  PubMed  CAS  Google Scholar 

  5. Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM (1992) Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med 176:587–592

    Article  PubMed  CAS  Google Scholar 

  6. Nelson PJ, Kim HT, Manning WC, Goralski TJ, Krensky AM (1993) Genomic organization and transcriptional regulation of the RANTES chemokine gene. J Immunol 151:2601–2612

    PubMed  CAS  Google Scholar 

  7. Kimata H, Yoshida A, Ishioka C, Fujimoto M, Lindley I, Furusho K (1996) RANTES and macrophage inflammatory protein 1 alpha selectively enhance immunoglobulin (IgE) and IgG4 production by human B cells. J Exp Med 183:2397–2402

    Article  PubMed  CAS  Google Scholar 

  8. Venge J, Lampinen M, Hakansson L, Rak S, Venge P (1996) Identification of IL-5 and RANTES as the major eosinophil chemoattractants in the asthmatic lung. J Allergy Clin Immunol 97:1110–1115

    Article  PubMed  CAS  Google Scholar 

  9. Lampinen M, Rak S, Venge P (1999) The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 29:314–322

    Article  PubMed  CAS  Google Scholar 

  10. Sato E, Simpson KL, Grisham MB, Koyama S, Robbins RA (1999) Effects of reactive oxygen and nitrogen metabolites on RANTES- and IL-5-induced eosinophil chemotactic activity in vitro. Am J Pathol 155:591–598

    PubMed  CAS  Google Scholar 

  11. Boyce JA (1997) The pathobiology of eosinophilic inflammation. Allergy Asthma Proc 18:293–300

    Article  PubMed  CAS  Google Scholar 

  12. McKenzie GJ, Bancroft A, Grencis RK, McKenzie AN (1998) A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Curr Biol 8:339–342

    Article  PubMed  CAS  Google Scholar 

  13. Donlon TA, Krensky AM, Wallace MR, Collins FS, Lovett M, Clayberger C (1990) Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12. Genomics 6:548–553

    Article  PubMed  CAS  Google Scholar 

  14. Liu H, Chao D, Nakayama EE, Taguchi H, Goto M, Xin X, Takamatsu JK, Saito H, Ishikawa Y, Akaza T, Juji T, Takebe Y, Ohishi T, Fukutake K, Maruyama Y, Yashiki S, Sonoda S, Nakamura T, Nagai Y, Iwamoto A, Shioda T (1999) Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci U S A 96:4581–4585

    Article  PubMed  CAS  Google Scholar 

  15. Nickel RG, Casolaro V, Wahn U, Beyer K, Barnes KC, Plunkett BS, Freidhoff LR, Sengler C, Plitt JR, Schleimer RP, Caraballo L, Naidu RP, Levett PN, Beaty TH, Huang SK (2000) Atopic dermatitis is associated with a functional mutation in the promoter of the C-C chemokine RANTES. J Immunol 164:1612–1616

    PubMed  CAS  Google Scholar 

  16. Fryer AA, Spiteri MA, Bianco A, Hepple M, Jones PW, Strange RC, Makki R, Tavernier G, Smilie FI, Custovic A, Woodcock AA, Ollier WE, Hajeer AH (2000) The −403 G→A promoter polymorphism in the RANTES gene is associated with atopy and asthma. Genes Immun 1:509–514

    Article  PubMed  CAS  Google Scholar 

  17. Yao TC, Kuo ML, See LC, Chen LC, Yan DC, Ou LS, Shaw CK, Huang JL (2003) The RANTES promoter polymorphism: a genetic risk factor for near-fatal asthma in Chinese children. J Allergy Clin Immunol 111:1285–1292

    Article  PubMed  CAS  Google Scholar 

  18. Al-Abdulhadi SA, Helms PJ, Main M, Smith O, Christie G (2005) Preferential transmission and association of the −403 G → A promoter RANTES polymorphism with atopic asthma. Genes Immun 6:24–30

    PubMed  CAS  Google Scholar 

  19. Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, MacIntyre NR, McKay RT, Wanger JS, Anderson SD, Cockcroft DW, Fish JE, Sterk PJ (2000) Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 161:309–329

    PubMed  CAS  Google Scholar 

  20. Sedgwick JB, Vrtis RF, Jansen KJ, Kita H, Bartemes K, Busse WW (2004) Peripheral blood eosinophils from patients with allergic asthma contain increased intracellular eosinophil-derived neurotoxin. J Allergy Clin Immunol 114:568–574

    Article  PubMed  CAS  Google Scholar 

  21. Backman A (1994) Skin tests for epidemiologic studies. Allergy 49:493–494

    Article  PubMed  CAS  Google Scholar 

  22. Brown WG, Halonen MJ, Kaltenborn WT, Barbee RA (1979) The relationship of respiratory allergy, skin test reactivity, and serum IgE in a community population sample. J Allergy Clin Immunol 63:328–335

    Article  PubMed  CAS  Google Scholar 

  23. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  PubMed  CAS  Google Scholar 

  24. Hedrick PW (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117:331–341

    PubMed  CAS  Google Scholar 

  25. Nelson PJ, Ortiz BD, Pattison JM, Krensky AM (1996) Identification of a novel regulatory region critical for expression of the RANTES chemokine in activated T lymphocytes. J Immunol 157:1139–1148

    PubMed  CAS  Google Scholar 

  26. Moriuchi H, Moriuchi M, Fauci AS (1997) Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES, a chemokine that blocks HIV infection. J Immunol 158:3483–3491

    PubMed  CAS  Google Scholar 

  27. Hizawa N, Yamaguchi E, Konno S, Tanino Y, Jinushi E, Nishimura M (2002) A functional polymorphism in the RANTES gene promoter is associated with the development of late-onset asthma. Am J Respir Crit Care Med 166:686–690

    Article  PubMed  Google Scholar 

  28. Choi SY, Sohn MH, Yum HY, Kwon BC, Kim KE (2005) Correlation between inhalant allergen-specific IgE and pulmonary function in children with asthma. Pediatr Pulmonol 39:150–155

    Article  PubMed  Google Scholar 

  29. Yang EG, Kim WJ, Kwon BC, Choi SY, Sohn MH, Kim KE (2006) Relationship among pulmonary function, bronchial hyperresponsiveness, and atopy in children with clinically stable asthma. Lung 184:73–79

    Article  PubMed  Google Scholar 

  30. Takada T, Suzuki E, Ishida T, Moriyama H, Ooi H, Hasegawa T, Tsukuda H, Gejyo F (2001) Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a Japanese population. Tissue Antigens 58:293–298

    Article  PubMed  CAS  Google Scholar 

  31. McDermott DH, Beecroft MJ, Kleeberger CA, Al-Sharif FM, Ollier WE, Zimmerman PA, Boatin BA, Leitman SF, Detels R, Hajeer AH, Murphy PM (2000) Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study. AIDS 14:2671–2678

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by a faculty research grant (No. 6-2004-97) of Yonsei University College of Medicine for 2004.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kyu-Earn Kim.

Additional information

Myung Hyun Sohn and Seung-Hyun Kim contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sohn, M.H., Kim, SH., Kim, KW. et al. RANTES Gene Promoter Polymorphisms Are Associated with Bronchial Hyperresponsiveness in Korean Children with Asthma. Lung 186, 37–43 (2008). https://doi.org/10.1007/s00408-007-9049-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-007-9049-3

Keywords

Navigation