Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis
Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis
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DOI：
10.1086/423942
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发表时间：
2004-10-01
影响因子：
6.4
通讯作者：
Osame, M
中科院分区：
文献类型：
--
作者：
Sabouri, AH;Saito, M;Osame, M
为了研究影响人类T细胞嗜淋巴细胞病毒（HTLV）I型感染结果的非人类白细胞抗原候选基因，我们分析了280例HTLV-I相关脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）患者和255例HTLV-I血清阳性无症状携带者白细胞介素（IL）-10启动子区的6个单核苷酸多态性。IL-10 - 592 A等位基因在Jurkat T细胞系中显示出比C等位基因更低的HTLV-I Tax诱导的转录活性，其与HAM/TSP发生的几率降低>2倍相关。（P= 0.011;比值比[OR]，0.50 [95%置信区间，0.30-0.86]）通过降低整个队列中的前病毒负荷（P= 0.009，方差分析）。考虑到IL-10 - 592 A的OR和观察到的频率，我们证明该等位基因可以预防44.7%（标准差，+/-13.1%）的HAM/TSP潜在病例，这表明它定义了队列中HAM/TSP遗传易感性的一个组成部分。
To investigate non-human leukocyte antigen candidate genes that influence the outcome of human T cell lymphotropic virus (HTLV) type I infection, we analyzed 6 single-nucleotide polymorphisms in the interleukin (IL)-10 promoter region in 280 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis(HAM/TSP) and 255 HTLV-I-seropositive asymptomatic carriers from an area where HTLV-I is endemic. The IL-10 -592 A allele, which shows lower HTLV-I Tax-induced transcriptional activity than the C allele in the Jurkat T cell line, was associated with a >2-fold reduction in the odds of developing HAM/TSP (P=.011; odds ratio [OR], 0.50 [95% confidence interval, 0.30-0.86]) by reducing the provirus load in the whole cohort (P=.009, analysis of variance). Given the OR and the observed frequency of IL-10 -592 A, we demonstrate that this allele prevents similar to44.7% (standard deviation, +/-13.1%) of potential cases of HAM/TSP, which indicates that it defines one component of the genetic susceptibility to HAM/TSP in the cohort.