This Article Full Text Full Text (PDF) All Versions of this Article: 200404-447OCv1 170/10/1057    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raby, B. A. Articles by Weiss, S. T. Search for Related Content PubMed PubMed Citation Articles by Raby, B. A. Articles by Weiss, S. T.

Association of Vitamin D Receptor Gene Polymorphisms with Childhood and Adult Asthma

Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, and Harvard Partners Center for Genomics and Genetics, Brigham and Women's Hospital; Division of Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center; Harvard Medical School; and Harvard School of Public Health, Boston, Massachusetts; and GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany

Correspondence and requests for reprints should be addressed to Benjamin Raby, M.D.C.M., M.P.H., Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115. E-mail: benjamin.raby{at}channing.harvard.edu

Vitamin D receptor (VDR) polymorphisms have been associated with several immune-related diseases, and VDR and vitamin D itself modulate T cell differentiation. VDR maps to chromosome 12q, near a region commonly linked to asthma. We evaluated VDR as part of a 12q positional candidate survey, and in response to observations of VDR polymorphism associations with asthma and atopy in a founder population of Quebec. Twenty-eight loci in 7 positional candidates (7 in VDR) were genotyped in 582 families. Whereas other candidates demonstrated no association, the VDR ApaI polymorphism 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). Sex-specific associations between multiple VDR polymorphisms and immunoglobulin E levels were also observed (p = 0.006–0.01). Asthma associations were replicated in a second cohort (517 females with asthma and 519 matched control subjects): 4 of 6 VDR variants demonstrated significant association (p = 0.02–0.04). The direction of association in this second cohort was opposite to the effects seen in the trios, but similar to findings in the Quebec study. These results suggest that VDR influences asthma and allergy susceptibility in a complex manner.

Key Words: association studies • asthma • genetics • replication • VDR

This article has been cited by other articles:

				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]