Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy.
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 (VDR) gene. Through interaction with VDR, 1,25-dihydroxyvitamin D3 mediates numerous biological activities, such as regulation of helper T-cell development and subsequent cytokine secretion profiles. Variants of the VDR 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 VDR, 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 VDR 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 < or = p < or = 0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004 < or = p < or = 0.01). The findings have been replicated by another research team in a second but not in a third cohort. These results identify VDR variants as genetic risk factors for asthma/atopy and implicate a non-human leukocyte antigen immunoregulatory molecule in the pathogenesis of asthma and atopy.
McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Audrey H
AH
Poon
Catherine
C
Laprise
Mathieu
M
Lemire
Alexandre
A
Montpetit
Donna
D
Sinnett
Erwin
E
Schurr
Thomas J
TJ
Hudson
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015995:Prevalence; D011792:Quebec / Q000453:epidemiology; D018167:Receptors, Calcitriol / Q000235:genetics*; D017678:Sex Distribution
D018167:Receptors, Calcitriol