1. ¹McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
2. ²Department of Biochemistry, McGill University, Montreal, QC, Canada
3. ³Université du Québec à Chicoutimi, 555 Boulevard Université, Chicoutimi, QC, Canada
4. ⁴Community Genomic Medicine Centre, University of Montreal, Chicoutimi Hospital, Chicoutimi, QC, Canada
5. ⁵McGill University and Genome Québec Innovation Centre, Montreal, QC, Canada
6. ⁶Department of Medicine and Human Genetics, McGill University, Montreal, QC, Canada

Correspondence: Dr E Schurr, Montreal General Hospital Research Institute, McGill Centre for the Study of Host Resistance, McGill University Health Centre, 1650 Cedar Avenue, Room L11-520, Montreal, QC, Canada H3G 1A4. E-mail: erwin@igloo.epi.mcgill.ca

Received 6 April 2005; Revised 20 May 2005; Accepted 23 May 2005; Published online 30 June 2005.

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'CA_n, 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.