A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis.
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis.
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作者：
toll样受体（TLRs）及其信号通路成员在启动针对多种病原体的先天免疫应答中发挥重要作用。接头蛋白TIRAP介导TLR-2和-4的下游信号传导。我们报告了一项来自冈比亚、肯尼亚、英国和越南的6106例侵袭性肺炎球菌病、菌血症、疟疾和结核病患者的病例对照遗传关联研究。33个snp进行基因分型，包括TIRAP S180L。发现该变异的杂合携带与不同研究人群中所有四种传染病独立相关（IPD的P=0.003， OR=0.59, 95%CI 0.42-0.83；菌血症的P=0.003， OR=0.40, 95%CI 0.21-0.77；疟疾的P=0.002， OR=0.47, 95%CI 0.28-0.76；结核病的P=0.008， OR=0.23, 95%CI 0.07-0.73）。当两个研究组合并时，观察到大量支持S180L杂合性对传染病的保护作用（N=6106，总体P≤9.6×10-8）。Tirap S180L也被证明在TLR2信号转导中功能受损。
Toll-like receptors (TLRs) and members of their signalling pathway play an important role in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein TIRAP mediates downstream signalling of TLR-2 and -4. We report a case-control genetic association study of 6106 individuals from Gambia, Kenya, United Kingdom, and Vietnam, with invasive pneumococcal disease, bacteraemia, malaria and tuberculosis. Thirty-three SNPs were genotyped, including TIRAP S180L. Heterozygous carriage of this variant was found to associate independently with all four infectious diseases in the different study populations (P=0.003, OR=0.59, 95%CI 0.42-0.83 for IPD; P=0.003, OR=0.40, 95%CI 0.21-0.77 for bacteraemia; P=0.002, OR=0.47, 95%CI 0.28-0.76 for malaria; P=0.008, OR=0.23 95%CI 0.07-0.73 for tuberculosis). Substantial support for a protective effect of S180L heterozygosity against infectious diseases was observed when the study groups were combined (N=6106, Overall P≤9.6×10-8). Tirap S180L was also shown to be functionally impaired in TLR2 signal transduction.
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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
DOI：
10.1084/jem.189.11.1777
发表时间：
1999-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shimazu R;Akashi S;Ogata H;Nagai Y;Fukudome K;Miyake K;Kimoto M
通讯作者：
Kimoto M
影响因子：
64.8
作者：
Horng, T;Barton, GM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
影响因子：
4.8
作者：
Dunne, A;Ejdebäck, M;Gay, NJ
通讯作者：
Gay, NJ