Du, RoseLitonjua, Augusto A.Tantisira, KelanLasky-Su, JessicaSunyaev, ShamilKlanderman, BarbaraCeledón, Juan C.Avila, LydianaSoto-Quiros, Manuel E.Weiss, Scott2016-05-162012Du, Rose, Augusto A. Litonjua, Kelan G. Tantisira, Jessica Lasky-Su, Shamil R. Sunyaev, Barbara J. Klanderman, Juan C. Celedón, Lydiana Avila, Manuel E. Soto-Quiros, and Scott T. Weiss. 2012. 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. Journal of Allergy and Clinical Immunology 129, no. 2: 368–373.e5. doi:10.1016/j.jaci.2011.09.034.0091-6749http://nrs.harvard.edu/urn-3:HUL.InstRepos:27003505Background— 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. Conclusion— 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.en-USgene-environment interactiongenome-wide association studyvitamin Dasthma exacerbationJournal Article2016-05-1610.1016/j.jaci.2011.09.034