Published ahead of print on July 28, 2004, doi:10.1164/rccm.200403-412OC
American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 967-973, (2004)
© 2004 American Thoracic Society
doi: 10.1164/rccm.200403-412OC
Association of Vitamin D Receptor Genetic Variants with Susceptibility to Asthma and Atopy
Audrey H. Poon,
Catherine Laprise,
Mathieu Lemire,
Alexandre Montpetit,
Donna Sinnett,
Erwin Schurr and
Thomas J. Hudson
McGill Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal; Université du Québec à Chicoutimi; Community Genomic Medicine Centre, University of Montreal, Chicoutimi Hospital, Chicoutimi; McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada
Correspondence and requests for reprints should be addressed to Thomas J. Hudson, M.D., McGill University and Genome Quebec Innovation Centre, 740 Penfield Avenue, Room 7105, Montreal, PQ, H3A 1A4 Canada. 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 (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  p 0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004 p 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.
Key Words: genetic predisposition • polymorphism • vitamin D receptor
This article has been cited by other articles:
|
|
|
|
 
J. M. Brehm, J. C. Celedon, M. E. Soto-Quiros, L. Avila, G. M. Hunninghake, E. Forno, D. Laskey, J. S. Sylvia, B. W. Hollis, S. T. Weiss, et al.
Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica
Am. J. Respir. Crit. Care Med.,
May 1, 2009;
179(9):
765 - 771.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Dmitrieva, C. A. Hinojos, M. L. Grove, R. J. Bell, E. Boerwinkle, M. Fornage, and P. A. Doris
Genome-Wide Identification of Allelic Expression in Hypertensive Rats
Circ Cardiovasc Genet,
April 1, 2009;
2(2):
106 - 115.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Chatzi, G Apostolaki, M Kogevinas, and P Cullinan
Authors' reply
Thorax,
May 1, 2008;
63(5):
474 - 475.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Begin, K. Tremblay, D. Daley, M. Lemire, S. Claveau, C. Salesse, S. Kacel, A. Montpetit, A. Becker, M. Chan-Yeung, et al.
Association of Urokinase-type Plasminogen Activator with Asthma and Atopy
Am. J. Respir. Crit. Care Med.,
June 1, 2007;
175(11):
1109 - 1116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Bosse, K. Maghni, and T. J. Hudson
1{alpha},25-Dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes
Physiol Genomics,
April 24, 2007;
29(2):
161 - 168.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A Camargo Jr, S. L Rifas-Shiman, A. A Litonjua, J. W Rich-Edwards, S. T Weiss, D. R Gold, K. Kleinman, and M. W Gillman
Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age
Am. J. Clinical Nutrition,
March 1, 2007;
85(3):
788 - 795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Devereux, A. A Litonjua, S. W Turner, L. C. Craig, G. McNeill, S. Martindale, P. J Helms, A. Seaton, and S. T Weiss
Maternal vitamin D intake during pregnancy and early childhood wheezing
Am. J. Clinical Nutrition,
March 1, 2007;
85(3):
853 - 859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jaradat, C. Stapleton, S. L. Tilley, D. Dixon, C. J. Erikson, J. G. McCaskill, H. S. Kang, M. Angers, G. Liao, J. Collins, et al.
Modulatory Role for Retinoid-related Orphan Receptor {alpha} in Allergen-induced Lung Inflammation
Am. J. Respir. Crit. Care Med.,
December 15, 2006;
174(12):
1299 - 1309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Li, P. Hener, Z. Zhang, S. Kato, D. Metzger, and P. Chambon
Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis
PNAS,
August 1, 2006;
103(31):
11736 - 11741.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Pastinen, B. Ge, S. Gurd, T. Gaudin, C. Dore, M. Lemire, P. Lepage, E. Harmsen, and T. J. Hudson
Mapping common regulatory variants to human haplotypes
Hum. Mol. Genet.,
December 15, 2005;
14(24):
3963 - 3971.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Fabbri, S. P. Peters, I. Pavord, S. E. Wenzel, S. C. Lazarus, W. MacNee, F. Lemaire, and E. Abraham
Allergic Rhinitis, Asthma, Airway Biology, and Chronic Obstructive Pulmonary Disease in AJRCCM in 2004
Am. J. Respir. Crit. Care Med.,
April 1, 2005;
171(7):
686 - 698.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Raby, R. Lazarus, E. K. Silverman, S. Lake, C. Lange, M. Wjst, and S. T. Weiss
Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma
Am. J. Respir. Crit. Care Med.,
November 15, 2004;
170(10):
1057 - 1065.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2004 American Thoracic Society
|
|
|
