Published ahead of print on July 28, 2004, doi:10.1164/rccm.200404-447OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 10, November 2004, 1057-1065
A more recent version of this article appeared on November 15, 2004
Submitted on April 2, 2004
Accepted on July 27, 2004
Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma
Benjamin A Raby1*, Ross Lazarus2, Edwin K Silverman3, Steven Lake2, Christoph Lange4, Mathias Wjst5, and Scott T Weiss6
1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA,
2 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States,
3 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA,
4 Harvard School of Public Health, Boston, MA, USA,
5 Institute of Epidemiology, GSF National Research Center for Environmental Health, Neuherberg, Germany,
6 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, USA; Harvard Partners Center for Genomics, USA
* To whom correspondence should be addressed. E-mail: rebar{at}channing.harvard.edu.
Vitamin D receptor (VDR) polymorphisms have been associated with immune-related diseases, and the receptor and Vitamin D itself are important in T-cell differentiation. We undertook a positional candidate strategy for asthma susceptibility genes in a linkage region on chromosome 12q that includes VDR. 582 families from the Childhood Asthma Management Program (CAMP) were genotyped at 28 loci from seven positional candidate genes, including seven VDR polymorphisms. The VDR ApaI polymorphism (rs7975232) demonstrated significant transmission distortion, with undertransmission of the C allele in a ratio of 4:5 (p=0.01). This association was most prominent in girls, in whom distortion was more marked (p=0.009). Gender-specific associations were detected for quantitative traits, with multiple VDR polymorphisms demonstrating association with serum Immunoglobulin E levels (p=0.006-0.01). Replication of associations between asthma and VDR was observed in 517 female asthmatics and 519 matched controls ascertained through the Nurses Health Study. 4 of 6 variants typed demonstrated significant evidence of association with asthma (p=0.02-0.04). The direction of association in this second study was opposite to the effects seen in the trios, but similar to the findings in the Quebec study of Poon et al. These results suggest that VDR influences asthma and allergy susceptibility in a complex manner.
Key words: asthma, genetics, vitamin D receptor, association studies, replication
This article has been cited by other articles:
|
|
|
|
 
M. Li, Z.-H. Miao, Z. Chen, Q. Chen, M. Gui, L.-P. Lin, P. Sun, Y.-H. Yi, and J. Ding
Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2{alpha} by unique interference with its DNA binding and catalytic cycle
Ann. Onc.,
September 22, 2009;
(2009)
mdp335v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Rogers, B. A. Raby, J. A. Lasky-Su, A. Murphy, R. Lazarus, B. J. Klanderman, J. S. Sylvia, J. P. Ziniti, C. Lange, J. C. Celedon, et al.
Assessing the Reproducibility of Asthma Candidate Gene Associations, Using Genome-wide Data
Am. J. Respir. Crit. Care Med.,
June 15, 2009;
179(12):
1084 - 1090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
M. A. Seibold, B. Wang, C. Eng, G. Kumar, K. B. Beckman, S. Sen, S. Choudhry, K. Meade, M. Lenoir, H. G. Watson, et al.
An african-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity
Hum. Mol. Genet.,
September 1, 2008;
17(17):
2681 - 2690.
[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]
|
|
|
|
|
|
|
S. T Weiss and A. A Litonjua
Maternal diet vs lack of exposure to sunlight as the cause of the epidemic of asthma, allergies and other autoimmune diseases
Thorax,
September 1, 2007;
62(9):
746 - 748.
[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]
|
|
|
|
|
|
|
P. J Stover
Influence of human genetic variation on nutritional requirements
Am. J. Clinical Nutrition,
February 1, 2006;
83(2):
436S - 442S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Raby, K. Van Steen, J. C. Celedon, A. A. Litonjua, C. Lange, S. T. Weiss, and for the CAMP Research Group
Paternal History of Asthma and Airway Responsiveness in Children with Asthma
Am. J. Respir. Crit. Care Med.,
September 1, 2005;
172(5):
552 - 558.
[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]
|
|
|
Copyright © 2004 American Thoracic Society
|
|
|
