Copy number variations of CCL3L1 and long-term prognosis of HIV-1 infection in asymptomatic HIV-infected Japanese with hemophilia
Copy number variations of CCL3L1 and long-term prognosis of HIV-1 infection in asymptomatic HIV-infected Japanese with hemophilia
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DOI：
10.1007/s00251-007-0252-4
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发表时间：
2007-10-01
期刊：
影响因子：
3.2
通讯作者：
Kimura, Akinori
中科院分区：
文献类型：
--
作者：
Nakajima, Toshiaki;Ohtani, Hitoshi;Kimura, Akinori
我们在1995年建立了一组感染艾滋病毒的、无症状的日本血友病患者进行随访研究。所有感染HIV-1超过10年的受试者在进入时都符合长期无进展(LTNPs)的标准；然而，他们中的一些人后来出现了淋巴细胞减少症，需要在另外五年的观察中接受抗逆转录病毒治疗。在这项研究中，我们研究了CCL3L1剂量对慢性HIV-1感染者长期预后的影响。我们收集了95名长期幸存者的基因组DNA，其中包括48名无进展者和47名接受抗逆转录病毒治疗的受试者。95例血友病HIV-1感染者与205例正常对照的CCL3L1基因拷贝数分布有显著差异。HIV-1感染者的CCL3L1平均拷贝数显著低于对照组(5.00±0.22vs3.35+/-0.24，p<；0.001)。此外，拥有两个或更少CCL3L1副本的受试者感染HIV-1的风险显著更高。在慢性HIV-1感染者中，CCL3L1拷贝数变异对疾病进展无显著影响(3.68+/-0.37vs3.02+/-0.29，ns)。此外，CCL3L1拷贝数的变化对其中HIV-1载量水平影响不大。我们得出结论，CCL3L1拷贝数的变化显然不是决定慢性HIV-1感染预后的因素，尽管它与HIV-1易感性有关。
We set up a cohort of HIV-infected, asymptomatic Japanese patients with hemophilia for follow-up study in 1995. All subjects who had been infected with HIV-1 for more than 10 years met the criteria for long-term non-progressors (LTNPs) at the time of entry; however, some of them later developed lymphopenia and required antiretroviral treatment during five more years of observation. In this study, we investigated the impacts of the CCL3L1 dose on the long-term prognosis in the subjects with chronic HIV-1 infection. We collected genomic DNA from 95 long-term survivors including 48 nonprogressors and 47 subjects receiving antiretroviral treatment. The distributions of CCL3L1 copy number significantly differed between the 95 HIV-1-infected subjects with hemophilia and 205 controls. Average copy number of CCL3L1 in the HIV-1-infected subjects was significantly lower than in control (5.00 +/- 0.22 vs 3.35 +/- 0.24, p < 0.001). Moreover, the subjects possessing two or less copies of CCL3L1 had significantly higher risk of acquiring HIV-1. However, CCL3L1 copy number variations had no significant effect on the disease progression among the LTNP subjects who had been afflicted with chronic HIV-1 infection for more than 15 years, when compared between nonprogressors and patients under treatment (3.68 +/- 0.37 vs 3.02 +/- 0.29, ns). Furthermore, variations in the CCL3L1 copy number had little effect on the levels of HIV-1 load among them. We conclude that variation in the CCL3L1 copy number is apparently not a factor that determines the prognosis of chronic HIV-1 infection, even though it is linked to HIV-1 susceptibility.