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Sex-specific effect of IL9 polymorphisms on lung function and polysensitization

Genes & Immunity volume 10, pages 559–565 (2009)Cite this article

Abstract

Sex differences in asthma-associated phenotypes are well known but the genetic factors that may account for these differences have received little attention. This study aimed to characterize sex-specific and pleiotropic genetic factors underlying four quantitative phenotypes involved in the main asthma physiopathological pathways: immunoglobulin E levels, a measure of polysensitization (SPTQ), eosinophil counts and a measure of lung function FEV1/H2 (forced expiratory volume in one second divided by height square). Sex-stratified univariate and bivariate linkage analyses were conducted in 295 families from the Epidemiological study on the Genetics and Environment of Asthma study. We found genome-wide significant evidence for a male-specific pleiotropic QTL (quantitative trait loci) on 5q31 (P=7 × 10−9) influencing both FEV1/H2 and SPTQ and for a female-specific pleiotropic QTL on 11q23 underlying SPTQ and immunoglobulin E (P=2 × 10−5). Three other sex-specific regions of linkage were detected for eosinophil: 4q24 and 22q13 in females, and 3p25 in males. Further, bivariate association analysis of FEV1/H2 and SPTQ with 5q31 candidate genes in males showed a significant association with two single-nucleotide polymorphisms within IL9 gene, rs2069885 and rs2069882 (P=0.02 and P=0.002, respectively, after Bonferroni's correction). This study underlies the importance of taking into account complex mechanisms, such as heterogeneity according to sex and pleiotropy to unravel the genes involved in asthma phenotypes.

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Acknowledgements

The study was funded by INSERM, the French Ministry of Higher Education and Research, University of Evry, the French Agency for Environmental and Occupational Health Safety (Afsset-APR-SE-2004), Fondation pour la Recherche Médicale (ACE20061209064), the French National Agency for Research (ANR 05-SEST-020-02/05-9-97 and ANR 06-CEBS-029-02) and the European Commission as part of GABRIEL, a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community (Contract no. 01896 under the Integrated Programme LSH-2004-1.2.5-1 Post-genomic approaches to understand the molecular bias of asthma aiming at a preventive or therapeutic control).

Author information

Author notes

  1. H Aschard, E Bouzigon, E Corda, A Ulgen, M-H Dizier, F Gormand, M Lathrop, F Kauffmann and F Demenais: Details of the EGEA cooperative group are given in the appendix.

Authors and Affiliations

  1. INSERM, U946, Paris, France

    H Aschard, E Bouzigon, E Corda, A Ulgen & F Demenais

  2. Fondation Jean Dausset-CEPH, Paris, France

    H Aschard, E Bouzigon, E Corda, A Ulgen, M Lathrop & F Demenais

  3. Université Paris Diderot, Paris, France

    H Aschard, E Bouzigon, A Ulgen & F Demenais

  4. INSERM, U535, Villejuif, France

    M-H Dizier

  5. Université Paris-Sud 11, Villejuif, France

    M-H Dizier & F Kauffmann

  6. Centre Hospitalier Lyon-Sud, Pierre-B, é, nite, France

    F Gormand

  7. INSERM, U628, Lyon, France

    F Gormand

  8. Commissariat à l'Energie Atomique, Institut de G,

    M Lathrop

  9. é,

    M Lathrop

  10. nomique, Centre National de G,

    M Lathrop

  11. é,

    M Lathrop

  12. notypage, Evry, France

    M Lathrop

  13. INSERM, U780, Villejuif, France

    F Kauffmann

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Consortia

on behalf of the EGEA cooperative group

Corresponding author

Correspondence to H Aschard.

Appendix

Appendix

EGEA cooperative group

Coordination: F Kauffmann; F Demenais (genetics); I Pin (clinical aspects).

Respiratory epidemiology: Inserm U 700, Paris M Korobaeff (Egea1), F Neukirch (Egea1); Inserm U 707, Paris: I Annesi-Maesano; Inserm U 780, Villejuif: F Kauffmann, N Le Moual, R Nadif, MP Oryszczyn; Inserm U 823, Grenoble: V Siroux.

Genetics: Inserm U 393, Paris: J Feingold; Inserm U 535, Villejuif: MH Dizier; Inserm U 946, Paris: E Bouzigon, F Demenais; CNG, Evry: I Gut, M Lathrop.

Clinical centers: Grenoble: I Pin, C Pison; Lyon: D Ecochard (Egea1), F Gormand, Y Pacheco; Marseille: D Charpin (Egea1), D Vervloet; Montpellier: J Bousquet; Paris Cochin: A Lockhart (Egea1), R Matran (now in Lille); Paris Necker: E Paty, P Scheinmann; Paris-Trousseau: A Grimfeld, J Just.

Data and quality management: Inserm ex-U155 (Egea1): J Hochez; Inserm U 780, Villejuif: N Le Moual, C Ravault; Inserm U 946: N Chateigner; Grenoble: J Ferran.

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Aschard, H., Bouzigon, E., Corda, E. et al. Sex-specific effect of IL9 polymorphisms on lung function and polysensitization. Genes Immun 10, 559–565 (2009). https://doi.org/10.1038/gene.2009.46

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