Abstract
Reduced infection by mycobacteria, including Mycobacterium tuberculosis, may be partly responsible for increased prevalence of allergic and autoimmune diseases in developed countries. In a murine model of innate resistance to mycobacteria, the Nramp1 gene has been shown to affect asthma susceptibility. From this observation, it was proposed that human NRAMP1 may be a modulator of asthma risk in human populations. To experimentally test the candidacy of NRAMP1 in asthma susceptibility, we characterized five genetic variants of NRAMP1 (5′CAn, 274C>T, 469+14G>C, D543N, and 1729+del4) in an asthma family-based cohort from northeastern Quebec. We did not observe any significant association between NRAMP1 variants (either allele or haplotype specific) with asthma, atopy, or serum immunoglobulin E levels. These results demonstrate that, in spite of direct involvement of Nramp1 in a murine asthma model, in human populations NRAMP1 is not likely to be a major contributor to the genetic etiology of asthma and asthma-related phenotypes.
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Acknowledgements
We thank all families for their enthusiastic participation in this study. We would like to thank D Gagné and P Bégin for their invaluable participation in the ascertainment of the subjects. We thank Y Renaud, M Girard, and A Verville for technical assistance. We thank A Alcaïs (INSERM U550, Paris) for his comments on statistical analysis. This study was supported by the Canadian Genetic Diseases Network—Network Centres of Excellence (CGDN – NCE). C Laprise is supported by the Fonds pour la recherche en santé du Québec (FRSQ). TJ Hudson is recipient of an Investigator Award from CIHR and a Clinician-Scientist Award in Translational Research from the Burroughs Wellcome Fund. E Schurr is an Investigator of the Canadian Institutes of Health Research.
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Poon, A., Laprise, C., Lemire, M. et al. NRAMP1 is not associated with asthma, atopy, and serum immunoglobulin E levels in the French Canadian population. Genes Immun 6, 519–527 (2005). https://doi.org/10.1038/sj.gene.6364238
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DOI: https://doi.org/10.1038/sj.gene.6364238