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Free Content Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians

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SETTING: Host defense factors may influence the development of active tuberculosis (TB).

OBJECTIVE: To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB.

METHODS: A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and sex.

RESULTS: Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] × rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] × rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] × rs1816702, P = 0.005).

CONCLUSIONS: No association was detected with 5′(GT)n promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3′ TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race.

Keywords: SLC11A1; epistasis; genetic epidemiology; innate immunity; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Dr John T Macdonald Foundation Department of Human Genetics & Miami Institute of Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, USA 2: Division of Infectious Diseases, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas ‘Norberto Quirno’ (CEMIC), Buenos Aires, Argentina 3: Department of Medicine, Hospital F J Muñiz, Buenos Aires, Argentina 4: Duke University Medical Center, Durham, North Carolina, USA 5: Duke University Medical Center, Durham, North Carolina, USA; and Family Health International, Research Triangle Park, Durham, North Carolina, USA

Publication date: September 1, 2009

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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