Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans.
Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans.
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DOI：
10.1007/s00439-009-0741-7
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发表时间：
2010-01
期刊：
影响因子：
5.3
通讯作者：
Scott WK
中科院分区：
文献类型：
--
作者：
Velez DR;Wejse C;Stryjewski ME;Abbate E;Hulme WF;Myers JL;Estevan R;Patillo SG;Olesen R;Tacconelli A;Sirugo G;Gilbert JR;Hamilton CD;Scott WK
结核病（TB）是一个全球性的公共卫生问题，也是每年可预防的死亡的一个来源，2005年全世界有880万结核病新发病例和160万死亡病例。大约10%的感染者发展为肺结核或肺外结核，这表明宿主防御因素影响活动性疾病的发展。Toll样受体（TLR）多态性与TLR表达的调节和活动性TB的发展相关。在本研究中，从474名受试者中检测了TLR 1、TLR 2、TLR 4、TLR 6和TLR 9的71个多态性。（295例病例和179例对照）非裔美国人，381例（237例病例和144例对照）高加索人，从667（321例和346例对照）来自几内亚比绍的非洲人与肺结核的相关性，使用广义估计方程和逻辑回归。在TLR 9和TLR 2的人群中观察到统计学显著相关性。相关性的最强证据来自TLR 2的插入（I）/缺失（D）多态性（−196至−174），该多态性与白人（II vs. ID&DD，OR=0.41 [95%CI 0.24-0.68]，p=0.0007）和非洲人（II vs. ID&DD，OR=0.70 [95%CI 0.51-0.95]，p=0.023）的结核病相关。我们在三个独立人群样本中的发现表明，TLR 2和TLR 9的变异可能在决定结核病易感性方面发挥重要作用。
Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor’ (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/deletion (D) polymorphism (−196 to −174) in TLR2 that associated with TB in both Caucasians (II vs. ID&DD, OR=0.41 [95% CI 0.24–0.68], p=0.0007) and Africans (II vs. ID&DD, OR=0.70 [95% CI 0.51–0.95], p=0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.
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