HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.
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DOI:
10.1371/journal.pone.0163153
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Huang L
Huang L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Auld E;Lin J;Chang E;Byanyima P;Ayakaka I;Musisi E;Worodria W;Davis JL;Segal M;Blackburn E;Huang L

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艾滋病毒感染是机会性肺炎(如结核病)和与年龄相关的健康并发症的危险因素。短端粒是生物衰老的标志,也与年龄相关疾病和死亡风险的增加有关。我们的目的是使用HIV感染和未感染的肺炎住院患者的单一队列来评估端粒长度缩短是否与HIV感染、结核病诊断和2个月死亡率相关。这是IHOP研究的一个子研究,一项前瞻性观察研究。参与者包括乌干达坎帕拉Mulago医院收治的184名成年人,他们接受了疑似结核病的评估,并随访了2个月。采用标准化问卷收集人口统计和临床数据。分离pbmc,用定量PCR测定端粒长度。评估了艾滋病毒感染、人口统计学和临床特征与端粒长度之间的关系,以及端粒长度、结核病诊断和2个月死亡率之间的关系。双变量分析中P≤0.2的变量被纳入多变量模型。在hiv感染者和未感染者之间没有观察到显著的人口统计学或临床差异。在双变量分析中,年龄较大(P<0.0001)、男性(P = 0.04)、吸烟总包年(P<0.001)、过去一年饮酒(P = 0.12)和哮喘(P = 0.08)均与端粒长度较短相关(P≤0.2)。在调整这五个变量的多变量分析中,hiv阳性参与者的端粒明显短于hiv阴性参与者(β = -0.0621, 95% CI -0.113至-0.011,P = 0.02)。缩短的端粒与结核病或短期死亡率无关。艾滋病毒感染与较短端粒之间的关联表明,艾滋病毒可能在细胞衰老和生物衰老中发挥作用,而较短的端粒可能与这一人群中与年龄相关的健康并发症有关。这些发现表明,需要进一步研究艾滋病毒对衰老的影响。
HIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality. This was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models. No significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001), male gender (P = 0.04), total pack-years smoked (P<0.001), alcohol consumption in the past year (P = 0.12), and asthma (P = 0.08) were all associated (P≤0.2) with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02). Shortened telomeres were not associated with TB or short-term mortality. The association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.
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