Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection
Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection
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DOI：
10.1016/j.imlet.2014.04.005
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发表时间：
2014-07-01
影响因子：
4.4
通讯作者：
Al-Jabri, A. A.
中科院分区：
文献类型：
--
作者：
Said, E. A.;Al-Yafei, F.;Al-Jabri, A. A.
背景：Toll样受体（TLR）是机体对包括HIV-1在内的各种感染的天然免疫应答的重要组成部分。TLR中的单核苷酸多态性（SNP）与CD 4 T细胞计数和HIV疾病进展相关。TLR 7（Gln 11 Leu）SNP显示与CD 4 T细胞计数的快速下降相关。TLR 9（1635 A/G）SNP与HIV感染者的CD 4 T细胞计数之间存在相关性，尽管与该SNP相关的结果仍存在争议。（Gln 11 Leu）和TLR 9（1635 A/G）SNP与HIV感染期间免疫系统损伤的关系，如通过平均CD 4 T细胞计数所反映的。共有63名HIV感染者和100名健康人（对照组）参加了这项研究。在通过聚合酶链式反应（PCR）扩增可能含有SNP的区域并对PCR产物进行测序后，分析上述SNP。结果：TLR 7（AA）基因型Gln与HAART控制病毒血症后CD 4 T细胞计数>400个/μ 1有相关趋势。此外，在HIV感染者的病毒血症期间，TLR 9 1635（GG）基因型与较低的平均CD 4 T细胞计数相关，TLR 9 1635（AG）基因型与较高的平均CD 4 T细胞计数显著相关。这项纵向研究的结果支持TLR 9（1635 A/G）基因型与CD 4 T细胞计数之间存在关联，这有助于澄清关于这种关联的有争议的结果。病毒血症期CD 4 T细胞计数可能与TLR 7（Gln 11 Leu）和TLR 9（1635 A/G）基因型的组合有关。这些结果可能有助于预测对免疫系统的损害，从而影响新的抗HIV策略的规划。(C)2014爱思唯尔有限公司版权所有。
Background: Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including HIV-1 infection. The single-nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated with a rapid decline of CD4T cell count. A relation between TLR9 (1635A/G) SNP and CD4T cells count in HIV-infected patients is suggested, although the outcome associated with this SNP is still controversial.Objectives: To determine the relation of the TLR7 (Gln11Leu) and TLR9 (1635A/G) SNPs with the damage to the immune system during HIV infection as reflected by the average CD4T cell count.Methods: A total of 63 HIV-infected patients and 100 healthy individuals (controls) were enrolled in this study. The above named SNPs were analyzed after amplification of the regions that potentially contain the SNPs by polymerase chain reaction (PCR) and sequencing of the PCR products. The frequency of these SNPs and their relation with the CD4T cell count were investigated.Results: The TLR7 (AA) genotype 'Gln' had a trend toward being associated with a CD4T cell count >400 cells/mu 1 after controlling viremia via HAART. Additionally, the TLR9 1635 (GG) genotype was associated with a low average CD4T cell count and the TLR9 1635 (AG) genotype was significantly related to a higher average CD4T cell count during the viremic period in HIV-infected patients.Conclusion: The results of this longitudinal study supports the presence of an association between the TLR9 (1635A/G) genotype and the CD4T cell count, which helps clarifying the controversial results regarding this association. It also suggests that the CD4T cell count during the viremic period might be linked to the combination of both TLR7 (Gln11Leu) and TLR9 (1635A/G) genotypes. These results may help predicting the damage to the immune system, and thus impacting the planning for novel anti-HIV strategies. (C) 2014 Elsevier B.V. All rights reserved.