Published ahead of print on July 28, 2004, doi:10.1164/rccm.200403-412OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 9, November 2004, 967-973
A more recent version of this article appeared on November 1, 2004
Submitted on April 2, 2004
Accepted on July 27, 2004
Association of Vitamin D Receptor Genetic Variants with Susceptibility to Asthma and Atopy
Audrey Poon1, Catherine Laprise2, Mathieu Lemire3, Alexandre Montpetit3, Donna Sinnett3, Erwin Schurr1, and Thomas J Hudson4*
1 McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada,
2 Universite du Quebec a Chicoutimi, Chicoutimi, Quebec, Canada; Community Genomic Medicine Centre, University of Montreal, Chicoutimi Hospital, Chicoutimi, Quebec, Canada,
3 McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada,
4 McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: tom.hudson{at}mcgill.ca.
Genome scans for asthma have identified suggestive or significant linkages on 17 different chromosomes, including chromosome 12, region q13-23, housing the vitamin D receptor gene. Through interaction with vitamin D receptor, 1,25-dihydroxyvitamin D3 mediates numerous biological activities; such as regulation of helper T cell development and subsequent cytokine secretion profiles. Variants of the vitamin D receptor have been found to be associated with immune-mediated diseases that are characterized by an imbalance in helper T cell development, such as Crohn's disease and tuberculosis. The vitamin D receptor, hence, is a good candidate to be investigated for association with asthma, which is characterized by enhanced helper T cell type 2 activity. Here, we examined vitamin D receptor genetic variants in an asthma family-based cohort from Quebec. We report six variants to be strongly associated with asthma and four with atopy (0.0005 p0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004p0.01). The findings have been replicated in a second, but not in a third cohort, by another research team. These results identify vitamin D receptor variants as genetic risk factors for asthma/atopy and implicate a non-HLA immunoregulatory molecule in the pathogenesis of asthma and atopy.
Key words: VDR, polymorphism, genetic predisposition
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