Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians
Abstract: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.
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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