Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA.
J Acquir Immune Defic Syndr. 2010 Aug;54(4):343-51. doi: 10.1097/QAI.0b013e3181deaf4d.
Approximately 10%-15% of patients with AIDS but without ocular opportunistic infections will have a presumed neuroretinal disorder (HIV-NRD), manifested by reduced contrast sensitivity and abnormal visual fields. The loss of contrast sensitivity often is sufficient to impair reading speed. To evaluate the effect of host genetics on HIV-NRD, we explored validated AIDS restriction gene variants CCR5Delta32, CCR2-64I, CCR5 P1, SDF-3'A, IL-10-5'A, RANTES -403A, RANTES -28G, RANTES-In1.1C, CX3CR1-249I, CX3CR1-280M, IFNG-179T, MDR1-3435T, and MCP-1364G, each of which has been implicated previously to influence HIV-1 infection, AIDS progression, therapy response, and antiviral drug metabolism, and an IL-10 receptor gene, IL-10R1, in the Longitudinal Study of the Ocular Complications of AIDS cohort. In European Americans (cases = 55, controls = 290), IL-10-5'A variant and its promoter haplotype (hazard ratio = 2.09, confidence interval. 1.19 to 3.67, P = 0.01), in African Americans (cases = 54, controls = 180), RANTES-In1.1C and the associated haplotype (hazard ratio = 2.72, confidence interval.: 1.48 to 5.00, P = 0.001), showed increased HIV-NRD susceptibility. Although sample sizes are small and P values do not pass a strict Bonferroni correction, our results suggest that, in European Americans, an IL-10-related pathway, and, in African Americans, chemokine receptor ligand polymorphisms in RANTES are risk factors for HIV-NRD development. Clearly, further studies are warrented.
大约 10%-15%的艾滋病患者但没有眼部机会性感染将有假定的神经视网膜疾病(HIV-NRD),表现为对比敏感度降低和视野异常。对比敏感度的丧失往往足以损害阅读速度。为了评估宿主遗传学对 HIV-NRD 的影响,我们探讨了经过验证的 AIDS 限制基因变体 CCR5Delta32、CCR2-64I、CCR5 P1、SDF-3'A、IL-10-5'A、RANTES-403A、RANTES-28G、RANTES-In1.1C、CX3CR1-249I、CX3CR1-280M、IFNG-179T、MDR1-3435T 和 MCP-1364G,其中每个基因先前都被认为会影响 HIV-1 感染、艾滋病进展、治疗反应和抗病毒药物代谢,以及 IL-10 受体基因 IL-10R1,在眼并发症艾滋病队列的纵向研究中。在欧洲裔美国人(病例=55,对照=290)中,IL-10-5'A 变体及其启动子单倍型(危险比=2.09,置信区间 1.19 至 3.67,P=0.01),在非裔美国人(病例=54,对照=180)中,RANTES-In1.1C 和相关的单倍型(危险比=2.72,置信区间 1.48 至 5.00,P=0.001),显示出增加的 HIV-NRD 易感性。尽管样本量较小且 P 值未通过严格的 Bonferroni 校正,但我们的结果表明,在欧洲裔美国人中,IL-10 相关途径,以及在非裔美国人中,RANTES 中的趋化因子受体配体多态性是 HIV-NRD 发展的危险因素。显然,需要进一步研究。