NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.
NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.
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DOI：
10.1007/s00439-009-0713-y
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发表时间：
2009-11
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;Hulme WF;Myers JL;Weinberg JB;Levesque MC;Stryjewski ME;Abbate E;Estevan R;Patillo SG;Gilbert JR;Hamilton CD;Scott WK
结核病在世界范围内有相当大的死亡率，接触结核病的人中有5%-10%进展为活动性结核病。对小鼠和人类的研究表明，诱导型一氧化氮合酶(INOS)分子在结核病免疫反应中发挥着重要作用。对726名有结核病、亲属或密切接触者对照的个体进行了一项混合病例对照研究(279例病例和166名对照非裔美国人；198例病例和123名对照高加索人)。从NOS2a基因中筛选出39个单核苷酸多态(SNPs)，利用广义估计方程进行单SNP、单倍型和多位点与其他类型候选基因的交互作用分析。在非裔美国人中，10个NOS2ASNP与结核病有关。相关性最强的是rs2274894(优势比OR=1.84，95%可信区间[1.23-2.77]，p=0.003)和rs7215373(优势比1.67，95%可信区间[1.17-2.37]，p=0.004)，这两个位点都通过了多次比较的错误发现率校正(q*=0.2)。NOS2Ars2248814和IFNGR1rs1327474之间的基因-基因交互作用最强(p=0.0004)，NOS2Ars944722和IFNGR1rs1327474之间的基因-基因交互作用最强(p=0.0006)。NOS2A中的另外3个SNP与TLR4 rs5030729相互作用，另外5个NOS2ASNP与IFNGR1 rs1327474相互作用。在高加索人中没有观察到明显的关联。这些结果表明，NOS2A变异可能导致结核病易感性，特别是在非洲人后裔中，并可能与TLR4和IFNGR1中的SNPs协同作用。
Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate (FDR) correction for multiple comparisons (q*=0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1.
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DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
影响因子：
5.3
作者：
Burgner, D;Usen, S;Kwiatkowski, DP
通讯作者：
Kwiatkowski, DP
影响因子：
3.2
作者：
Gomez, Luis Miguel;Anaya, Juan-Manuel;Martin, Javier
通讯作者：
Martin, Javier
DOI：
10.1164/rccm.200601-088oc
发表时间：
2006-08-01
影响因子：
24.7
作者：
Cooke, Graham S.;Campbell, Sarah J.;Hill, Adrian V. S.
通讯作者：
Hill, Adrian V. S.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y