1570. Variation in the Cytosolic DNA Recognition Molecule AIM2 is Associated with Pulmonary Tuberculosis in Vietnam
Session: Poster Abstract Session: Microbial and Host Genetic Factors in Disease
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
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  • Background: Understanding macrophage responses to Mycobacterium tuberculosis (MTb) infection may lead to novel vaccines and therapeutics for tuberculosis and other infectious diseases. The inflammasome is a multiprotein oligomer that initiates a caspase-dependent inflammatory cascade after immune recognition and is critical for control of MTb replication. AIM2, a cytosolic DNA recognition molecule, initiates inflammasome formation via the adaptor protein ASC and is critical for mycobacterial immunity in mice. However, AIM2’s importance in human immunity has not been well established. In this study, we examined whether common variants of AIM2 are associated with pulmonary tuberculosis in an adult Vietnamese Kinh population

    Methods: We used a case-population study design in Vietnam with cases of pulmonary tuberculosis.  We analyzed 4 haplotype-tagging SNPs in the AIM2 gene region.

    Results: 2 polymorphisms were associated with pulmonary tuberculosis. The missense SNP rs2276405 was associated with an increased risk of TB in a genotypic analysis (P=0.005).  The association fit a dominant model with an odds ratio of 2.2 (95% CI 1.31-3.67, P=0.001).  Another SNP, rs16841642, had a trend towards significance in a genotypic analysis (P=0.066) and was associated with protection from TB in a dominant model (odds ratio 0.72 (95% CI 0.54-0.96, P=0.022).  After a conservative Bonferroni correction for multiple comparisons, SNP rs2276405 remained associated with TB susceptibility.

    Conclusion: Our data demonstrates that AIM2 variation is associated with an increased risk of TB in Vietnam. Fine mapping studies are ongoing to identify the functional polymorphisms and immune mechanisms by which AIM2 variation alters human immunity to TB.  To our knowledge, this data is the first demonstration of an association of common genetic variants of AIM2 with any disease in humans.

    Javeed Shah, MD1, Nguyen Thuong2,3, Nguyen Thi Bich Yen4, Phan Vuong Khac Thai4, M CAWS2, Sarah Dunstan2,3 and Thomas Hawn, MD, PhD1, (1)Division of Infectious Diseases, University of Washington, Seattle, WA, (2)Centre for Tropical Medicine, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam, (3)Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford, United Kingdom, (4)Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam

    Disclosures:

    J. Shah, None

    N. Thuong, None

    N. T. B. Yen, None

    P. V. K. Thai, None

    M. CAWS, None

    S. Dunstan, None

    T. Hawn, None

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