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

Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians.
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DOI：
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发表时间：
2009-09
期刊：
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
影响因子：
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通讯作者：
Digna R. Velez;William Hulme;Jamie L. Myers;M. Stryjewski;Eduardo Abbate;R. Estevan;Sara G. Patillo;J. Gilbert;Carol Dukes Hamilton;William K. Scott
Digna R. Velez;William Hulme;Jamie L. Myers;M. Stryjewski;Eduardo Abbate;R. Estevan;Sara G. Patillo;J. Gilbert;Carol Dukes Hamilton;William K. Scott
中科院分区：
其他
文献类型：
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作者：
Digna R. Velez;William Hulme;Jamie L. Myers;M. Stryjewski;Eduardo Abbate;R. Estevan;Sara G. Patillo;J. Gilbert;Carol Dukes Hamilton;William K. Scott

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宿主防御因素可能影响活动性结核病的发展。目的检测溶质载体家族11 A成员1（SLC 11 A1）的变异体与结核病的相关性。方法采用混合病例对照研究方法，对474名非裔美国人（243个家族）和381名白人（192个家族）的肺结核病例、亲属或密切接触者对照进行研究，采用校正年龄和性别的广义估计方程，检测13个SLC 11 A1多态性与肺结核的相关性。结果在白人中观察到两种相关性（rs3731863，P = 0.03和rs 17221959，P = 0.04），在非洲裔美国人中观察到一种相关性（rs3731865，P = 0.05）。SLC 11 A1和11个结核病候选基因多态性的多位点分析检测了白种人SLC 11 A1和诱导型一氧化氮合酶（NOS 2A）之间的相互作用（rs3731863 [SLC11A1] × rs8073782 [NOS2A]，P = 0.009; rs3731863 [SLC 11 A1] x rs 17722851 [NOS 2A]，P = 0.007）和Toll样受体2（TLR 2）在非裔美国人中（rs3731865 [SLC 11 A1] x rs 1816702，P = 0.005）。结论：未检测到与SLC 11 A1低表达相关的5 '（GT）（n）启动子多态性rs 17235409（D543 N）或rs 17235416（3' TGTG插入/缺失多态性）。SLC 11 A1多态性rs3731865与非洲裔美国人的结核病相关，与先前在西非的发现一致。这些结果表明，SLC 11 A1的变异增加了对肺结核的易感性，并与其他因种族而异的变异相互作用。
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; rs3731863 [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.