title: Genome-wide association study reveals class I MHC-restricted T cell-associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations.
abstract: BACKGROUND
  It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility.
  
  
  OBJECTIVE
  We sought to find genetic factors that might interact with vitamin D levels to affect the risk of asthma exacerbation.
  
  
  METHODS
  We conducted a genome-wide study of gene-vitamin D interaction on asthma exacerbations using population-based and family-based approaches on 403 subjects and trios from the Childhood Asthma Management Program. Twenty-three polymorphisms with significant interactions were studied in a replication analysis in 584 children from a Costa Rican cohort.
  
  
  RESULTS
  We identified 3 common variants in the class I MHC-restricted T cell-associated molecule gene (CRTAM) that were associated with an increased rate of asthma exacerbations based on the presence of a low circulating vitamin D level. These results were replicated in a second independent population (unadjusted combined interaction, P = .00028-.00097; combined odds ratio, 3.28-5.38). One variant, rs2272094, is a nonsynonymous coding polymorphism of CRTAM. Functional studies on cell lines confirmed the interaction of vitamin D and rs2272094 on CRTAM expression. CRTAM is highly expressed in activated human CD8(+) and natural killer T cells, both of which have been implicated in asthmatic patients.
  
  
  CONCLUSIONS
  The findings highlight an important gene-environment interaction that elucidates the role of vitamin D and CD8(+) and natural killer T cells in asthma exacerbation in a genome-wide gene-environment interaction study that has been replicated in an independent population. The results suggest the potential importance of maintaining adequate vitamin D levels in subsets of high-risk asthmatic patients.
authors: Channing Laboratory, Brigham and Women's Hospital, Boston, Mass 02115, USA. rdu@partners.org
authors: Rose
authors: R
authors: Du
authors: Augusto A
authors: AA
authors: Litonjua
authors: Kelan G
authors: KG
authors: Tantisira
authors: Jessica
authors: J
authors: Lasky-Su
authors: Shamil R
authors: SR
authors: Sunyaev
authors: Barbara J
authors: BJ
authors: Klanderman
authors: Juan C
authors: JC
authors: Celedón
authors: Lydiana
authors: L
authors: Avila
authors: Manuel E
authors: ME
authors: Soto-Quiros
authors: Scott T
authors: ST
authors: Weiss
mesh_terms: D001249:Asthma / Q000097:blood / Q000235:genetics*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014807:Vitamin D / Q000097:blood*
chemical_list: D007136:Immunoglobulins; C408522:class-I restricted T cell-associated molecule; D014807:Vitamin D