The Journal of Allergy and Clinical Immunology
Volume 120, Issue 1 , Pages 84-90, July 2007

Polymorphisms in IL13, total IgE, eosinophilia, and asthma exacerbations in childhood

  • Gary M. Hunninghake, MD

      Affiliations

    • From the Channing Laboratory
    • Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston
    • Department of Medicine, Harvard Medical School, Boston
  • ,
  • Manuel E. Soto-Quirós, MD, PhD

      Affiliations

    • Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José
  • ,
  • Lydiana Avila, MD

      Affiliations

    • Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José
  • ,
  • Jessica Su, PhD

      Affiliations

    • From the Channing Laboratory
    • Department of Biostatistics, Harvard School of Public Health, Boston
  • ,
  • Amy Murphy, PhD

      Affiliations

    • From the Channing Laboratory
    • Department of Biostatistics, Harvard School of Public Health, Boston
  • ,
  • Dawn L. Demeo, MD, MPH

      Affiliations

    • From the Channing Laboratory
    • Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston
    • Department of Medicine, Harvard Medical School, Boston
  • ,
  • Ngoc P. Ly, MD, MPH

      Affiliations

    • From the Channing Laboratory
    • Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Massachusetts General Hospital for Children and Harvard Medical School, Boston
  • ,
  • Catherine Liang, MPH

      Affiliations

    • From the Channing Laboratory
  • ,
  • Jody S. Sylvia, BS

      Affiliations

    • From the Channing Laboratory
  • ,
  • Barbara J. Klanderman, PhD

      Affiliations

    • From the Channing Laboratory
    • Department of Medicine, Harvard Medical School, Boston
  • ,
  • Christoph Lange, PhD

      Affiliations

    • Department of Biostatistics, Harvard School of Public Health, Boston
  • ,
  • Benjamin A. Raby, MDCM, MPH

      Affiliations

    • From the Channing Laboratory
    • Department of Medicine, Harvard Medical School, Boston
    • Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston
  • ,
  • Edwin K. Silverman, MD, PhD

      Affiliations

    • From the Channing Laboratory
    • Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston
    • Department of Medicine, Harvard Medical School, Boston
  • ,
  • Juan C. Celedón, MD, DrPH

      Affiliations

    • From the Channing Laboratory
    • Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston
    • Department of Medicine, Harvard Medical School, Boston
    • Corresponding Author InformationReprint requests: Juan C. Celedón, MD, DrPH, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115.

Received 23 March 2007; received in revised form 23 April 2007; accepted 24 April 2007. published online 13 June 2007.

Boston, Mass, and San José, Costa Rica

Background

It is unclear whether single nucleotide polymorphisms (SNPs) in the gene for IL-13 (IL13) influence asthma severity and/or asthma morbidity.

Objectives

To examine the relation between IL13 SNPs and asthma-related phenotypes in 2 independent populations.

Methods

We used family-based methods to test for association between SNPs in IL13 and asthma-related phenotypes in Costa Rican children with asthma. We attempted to reproduce significant findings in white (non-Hispanic) children with asthma in the Childhood Asthma Management Program (CAMP).

Results

In Costa Rica and in CAMP, the A allele (Gln) of IL13 coding SNP (rs20541) was significantly associated with increased eosinophil count (P < .011 in both studies) and increased serum total IgE (P < .054 in both studies). The T allele of IL13 promoter SNP (rs1800925) was inversely associated with asthma exacerbations in Costa Rica (P = .069). Although this SNP (rs1800925) was not associated with asthma exacerbations among all white children in CAMP, it was associated with increased risk of asthma exacerbations among children on inhaled corticosteroids (P = .02).

Conclusion

Polymorphisms in IL13 were significantly associated with serum total IgE and eosinophil count in 2 populations. IL13 polymorphisms may also be associated with asthma exacerbations, and this effect may be dependent on medication use. Our study is the first to report a potential negative interaction between a genetic polymorphism and response to inhaled corticosteroids.

Clinical implications

Polymorphisms in IL13 are associated with serum total IgE and eosinophil count and may be associated with asthma exacerbations.

Key words: IL13, asthma, IgE, eosinophil, severity, exacerbations, Costa Rica, CAMP

Abbreviations used: CAMP, Childhood Asthma Management Program, FBAT, Family-based association test, FVC, Forced vital capacity, SNP, Single nucleotide polymorphism

 

 Supported by grants HL04370 and HL66289 from the National Institutes of Health. The CAMP Genetics Ancillary Study is supported by the National Heart, Lung, and Blood Institute, N01-HR-16049. Additional support for this research came from grants P50 HL67664 and T32 HL07427 from the National Institutes of Health and the National Heart, Lung, and Blood Institute.Disclosure of potential conflict of interest: E. K. Silverman has consulting arrangements with GlaxoSmithKline; has received grant support from GlaxoSmithKline; has received money for a talk on chronic obstructive pulmonary disease genetics from Wyeth; and has received honoraria from Bayer. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(07)00858-5

doi:10.1016/j.jaci.2007.04.032

The Journal of Allergy and Clinical Immunology
Volume 120, Issue 1 , Pages 84-90, July 2007