Leung Janice M, Fishbane Nick, Jones Meaghan, Morin Alexander, Xu Stella, Liu Joseph Cy, MacIsaac Julie, Milloy M-J, Hayashi Kanna, Montaner Julio, Horvath Steve, Kobor Michael, Sin Don D, Harrigan P Richard, Man S F Paul
Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
Division of Respiratory Medicine, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, V6Z 1Y6, Canada.
Aging (Albany NY). 2017 Feb 23;9(3):687-705. doi: 10.18632/aging.101184.
Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions. We measured changes in telomere length and DNA methylation in the peripheral blood of 31 intravenous drug users, who were followed longitudinally with blood samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), and at a later follow-up time (T3; 2.2±1 year from T2). Absolute telomere length measurements were performed using polymerase chain reaction methods. Methylation profiles were obtained using the Illumina Human Methylation450 platform. Methylation aging was assessed using the Horvath method. Telomere length significantly decreased between T1 and T2 (227±46 at T1 vs. 201±48 kbp/genome at T2, p=0.045), while no differences were observed between T2 and T3 (201±48 at T2 vs. 186±27 kbp/genome at T3, p=0.244). Methylation aging as measured by the age acceleration residual increased over the time course of HIV infection (p=0.035). CpG sites corresponding to and were differentially methylated between T1 and T2 at a q-value <0.05. Telomere shortening and methylation changes can therefore be observed in the short-term period immediately following HIV seroconversion. Further studies to confirm these results in larger sample sizes and to compare these results to non-HIV and non-injection drug users are warranted.
感染人类免疫缺陷病毒(HIV)的人群患与年龄相关疾病的风险增加。我们测量了31名静脉吸毒者外周血中端粒长度和DNA甲基化的变化,对他们进行纵向随访,在HIV感染前(T1)、HIV感染后即刻(T2;距T1 1.9±1年)以及之后的随访时间(T3;距T2 2.2±1年)采集血样。使用聚合酶链反应方法进行绝对端粒长度测量。使用Illumina Human Methylation450平台获得甲基化图谱。使用Horvath方法评估甲基化衰老。T1和T2之间端粒长度显著缩短(T1时为227±46,T2时为201±48 kbp/基因组,p = 0.045),而T2和T3之间未观察到差异(T2时为201±48,T3时为186±27 kbp/基因组,p = 0.244)。在HIV感染过程中,通过年龄加速残差测量的甲基化衰老增加(p = 0.035)。在q值<0.05时,与 和 对应的CpG位点在T1和T2之间存在差异甲基化。因此,在HIV血清转化后的短期内可以观察到端粒缩短和甲基化变化。有必要进行进一步研究,以更大样本量证实这些结果,并将这些结果与未感染HIV和非注射吸毒者进行比较。