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

D. R. Velez; W. F. Hulme; J. L. Myers; M. E. Stryjewski; E. Abbate; R. Estevan; S. G. Patillo; J. R. Gilbert; C. D. Hamilton; William K. Scott

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

D. R. Velez, W. F. Hulme, J. L. Myers, M. E. Stryjewski, E. Abbate, R. Estevan, S. G. Patillo, J. R. Gilbert, C. D. Hamilton, William K. Scott

Hussman Institute for Human Genomics

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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] x rs8073782 [NOS2A],P = 0.009; rs 3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x 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.

Original language	English (US)
Pages (from-to)	1068-1076
Number of pages	9
Journal	International Journal of Tuberculosis and Lung Disease
Volume	13
Issue number	9
State	Published - Sep 2009

Keywords

Epistasis
Genetic epidemiology
Innate immunity
SLC11A1
Tuberculosis

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Infectious Diseases

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Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians. / Velez, D. R.; Hulme, W. F.; Myers, J. L.; Stryjewski, M. E.; Abbate, E.; Estevan, R.; Patillo, S. G.; Gilbert, J. R.; Hamilton, C. D.; Scott, William K.

In: International Journal of Tuberculosis and Lung Disease, Vol. 13, No. 9, 09.2009, p. 1068-1076.

Research output: Contribution to journal › Article › peer-review

Velez, D. R. ; Hulme, W. F. ; Myers, J. L. ; Stryjewski, M. E. ; Abbate, E. ; Estevan, R. ; Patillo, S. G. ; Gilbert, J. R. ; Hamilton, C. D. ; Scott, William K. / Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians. In: International Journal of Tuberculosis and Lung Disease. 2009 ; Vol. 13, No. 9. pp. 1068-1076.

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title = "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] x rs8073782 [NOS2A],P = 0.009; rs 3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x 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 = "Epistasis, Genetic epidemiology, Innate immunity, SLC11A1, Tuberculosis",

author = "Velez, {D. R.} and Hulme, {W. F.} and Myers, {J. L.} and Stryjewski, {M. E.} and E. Abbate and R. Estevan and Patillo, {S. G.} and Gilbert, {J. R.} and Hamilton, {C. D.} and Scott, {William K.}",

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T1 - Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians

AU - Velez, D. R.

AU - Hulme, W. F.

AU - Myers, J. L.

AU - Stryjewski, M. E.

AU - Abbate, E.

AU - Estevan, R.

AU - Patillo, S. G.

AU - Gilbert, J. R.

AU - Hamilton, C. D.

AU - Scott, William K.

PY - 2009/9

Y1 - 2009/9

N2 - 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] x rs8073782 [NOS2A],P = 0.009; rs 3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x 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.

AB - 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] x rs8073782 [NOS2A],P = 0.009; rs 3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x 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.

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KW - Genetic epidemiology

KW - Innate immunity

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KW - Tuberculosis

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