Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection
Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection
复制标题
DOI：
10.1097/qad.0b013e328012b8ac
复制
发表时间：
2007-02-01
期刊：
影响因子：
3.8
通讯作者：
Aderem, Alan
中科院分区：
文献类型：
--
作者：
Bochud, Pierre-Yves;Hersberger, Martin;Aderem, Alan
背景：HIV-1感染的临床过程在个体之间是高度可变的，至少部分是由于宿主的遗传多态性。toll样受体（TLRs）在先天免疫中起着关键作用，编码这些受体的基因突变与感染易感性的增加或减少有关。目的：探讨TLR2-4和TLR7-9的单核苷酸多态性是否影响HIV-1感染的自然过程。方法：分析来自瑞士HIV队列研究的haart初始HIV阳性患者中tlr中的28个snp。使用Sequenom技术检测snp。利用期望最大化算法推断单倍型。使用最小二乘回归计算CD4 T细胞下降。CD4细胞快速下降，低于15个百分位数的患者被定义为快速进展。使用逻辑回归模型估计与snp相关的快速进展风险。其他可能的危险因素包括年龄、性别和危险群体（异性恋、同性恋和静脉注射毒品）。结果：TLR9中连锁不平衡的两个snp （1635A/G和+11746/A）与快速进展表型相关：对于1635A/G， GA与AA的比值比（OR）为3.9[95%可信区间（CI），1.7-9.2]， GG与AA的比值比（OR）为4.7 (95% CI,1.9-12.0) （P=0.0008）。结论：HIV-1感染的快速进展与TLR9多态性有关。由于其对干预策略和疫苗开发的潜在影响，需要进一步的流行病学和实验研究来证实这种关联。(c) 2007年Lippincott Williams & Wilkins。
Background: The clinical course of HIV-1 infection is highly variable among individuals, at least in part as a result of genetic polymorphisms in the host. Toll-like receptors (TLRs) have a key role in innate immunity and mutations in the genes encoding these receptors have been associated with increased or decreased susceptibility to infections.Objectives: To determine whether single-nucleotide polymorphisms (SNPs) in TLR2-4 and TLR7-9 influenced the natural course of HIV-1 infection.Methods: Twenty-eight SNPs in TLRs were analysed in HAART-naive HIV-positive patients from the Swiss HIV Cohort Study. The SNPs were detected using Sequenom technology. Haplotypes were inferred using an expectation-maximization algorithm. The CD4 T cell decline was calculated using a least-squares regression. Patients with a rapid CD4 cell decline, less than the 15th percentile, were defined as rapid progressors. The risk of rapid progression associated with SNPs was estimated using a logistic regression model. Other candidate risk factors included age, sex and risk groups (heterosexual, homosexual and intravenous drug use).Results: Two SNPs in TLR9(1635A/G and +11746/A) in linkage disequilibrium were associated with the rapid progressor phenotype: for 1635A/G, odds ratio (OR), 3.9 [95% confidence interval (CI),1.7-9.2] for GA versus AA and OR, 4.7 (95% CI,1.9-12.0) for GG versus AA (P=0.0008).Conclusion: Rapid progression of HIV-1 infection was associated with TLR9 polymorphisms. Because of its potential implications for intervention strategies and vaccine developments, additional epidemiological and experimental studies are needed to confirm this association. (c) 2007 Lippincott Williams & Wilkins.