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Association study between the CX3CR1 gene and asthma

Genes & Immunity volume 7, pages 632–639 (2006)Cite this article

Abstract

CX3CR1, a fractalkine receptor, mediates cell-adhesive and migratory functions in inflammation. Based on CX3CR1 expression observed in bronchial tissues of asthmatic subjects, we hypothesized that genetic variation at this locus may affect susceptibility to asthma. We carried out an association study and a haplotypic analysis with selected polymorphisms of the CX3CR1 in a familial asthmatic sample from a founder population. Genetic analyses performed by FBAT software showed five CX3CR1 single nucleotide polymorphisms (rs938203, rs2669849, rs1050592, T280M and V249I) with significant associations between their common alleles and asthma (P<0.004) in a dominant model. A haplotype formed with common alleles of rs1050592, T280M and V249I is also overtransmitted in asthmatic subjects (P=0.005) under a dominant model. The associations of V249I and rs2669849 have been validated in an independent case–control sample. For V249I, odds ratios (OR) are 2.16 (common homozygous) and 2.11 (heterozygous) in dominant model (P=0.031). For rs2669849, OR are 2.75 (common homozygous) and 1.86 (heterozygous) in additive model (P=0.007) and dominant model (P=0.059). These results suggest an asthma protective effect of the minor alleles in healthy control carriers. Further functional studies of CX3CR1 are needed to document its role in the pathophysiology of asthma.

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Acknowledgements

We thank all families of the SLSJ population for their enthusiastic participation in this study. We also thank Paul Bégin, Jean-Pierre Leblanc, Christian Allard, Mario Laforte, Hélène Archibald and Diane Gagné for their invaluable participation in the ascertainment of subjects, and Nathalie Pagé from the Laval Hospital for her manuscript revision. K Tremblay and V Provost are supported by the Respiratory Health Network (RHN) of the Fonds de la recherche en santé du Québec (FRSQ). K Tremblay is also supported by a grant from AllerGen (to TJ Hudson, A Sandford and C Laprise). TJ Hudson is the recipient of an Investigator Award from the Canadian Institutes of Health Research (CIHR) and a Clinician-scientist Award in Translational Research from the Burroughs Wellcome Fund. A Sandford is the chairholder of the Canadian Research Chair (www.chairs.gc.ca) on genetic susceptibility to inflammatory airway diseases. C Laprise is the chairholder of the Canada Research Chair on genetic determinants in asthma and the director of the Genetics & Genomics Thematic Unit of the RHN of the FRSQ. This work was supported by the Canadian Institutes of Health Research (CIHR) and the Respiratory Health Network (RHN) of the Fonds de la recherche en santé du Québec (FRSQ).

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Authors and Affiliations

  1. Department of Medicine, University of Montreal Community Genomic Medicine Centre, Chicoutimi University Hospital, Saguenay, Québec, Canada

    K Tremblay & C Laprise

  2. Department of Medicine, Hôpital Laval, Institut universitaire de cardiologie et de pneumologie de l'Université Laval, Québec, Québec, Canada

    K Tremblay, V Provost & M Laviolette

  3. Department of Medicine and Human Genetics, McGill University and Genome Québec Innovation Centre, Montreal, Québec, Canada

    M Lemire, T Pastinen, Y Renaud & T J Hudson

  4. James Hogg iCapture Centre, University of British Columbia, Vancouver, British Columbia, Canada

    A J Sandford

  5. Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Saguenay, Québec, Canada

    C Laprise

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  1. K Tremblay
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Correspondence to C Laprise.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Tremblay, K., Lemire, M., Provost, V. et al. Association study between the CX3CR1 gene and asthma. Genes Immun 7, 632–639 (2006). https://doi.org/10.1038/sj.gene.6364340

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