Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles (UCLA), Los Angeles, CA 90095, United States; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, United States.
EBioMedicine. 2022 Sep;83:104206. doi: 10.1016/j.ebiom.2022.104206. Epub 2022 Aug 6.
Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH.
Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV/FVC<0.70, and FEV decline over 6 years in blood.
The airway epithelium of PLWH with COPD was associated with greater GrimAge residuals compared to PLWH without COPD (Beta=3.18, 95%CI=1.06-5.31, P=0.005). In blood, FEV/FVC<LLN was associated with greater GrimAge residuals (Beta=1.74, 95%CI=0.37-3.24, P=0.019). FEV decline was inversely correlated with GrimAge residuals in blood (r=-0.13, P=0.012). PLWH who had normal lung function but who subsequently developed an FEV/FVC<0.70 over the course of 6 years had higher GrimAge residuals at baseline (Beta=2.33, 95%CI=0.23-4.44, P=0.031).
GrimAge may reflect lung and systemic epigenetic changes that occur with advanced airflow obstruction and may help to identify PLWH with a higher risk of developing COPD.
Canadian Institutes of Health Research and the British Columbia Lung Association. The START substudy was funded by NIH grants: UM1-AI068641, UM1-AI120197, and RO1HL096453.
年龄相关的合并症，如慢性阻塞性肺疾病（COPD），在感染人类免疫缺陷病毒（PLWH）的人群中很常见。我们研究了 COPD 与 PLWH 气道上皮和外周血的表观遗传年龄之间的关系。
从圣保罗医院 HIV 支气管镜队列中招募的 34 名 PLWH 的气道上皮刷检和从战略时机抗逆转录病毒治疗（START）研究中招募的 378 名 PLWH 的外周血进行 DNA 甲基化分析。计算了两个组织区室中年龄和健康跨度的 DNA 甲基化生物标志物 GrimAge。我们测试了 GrimAge 与气道上皮中的 COPD 以及血液中定义的 FEV/FVC<0.70 和 6 年内 FEV 下降的气流阻塞之间的关联。
与无 COPD 的 PLWH 相比，有 COPD 的 PLWH 的气道上皮与更大的 GrimAge 残差相关（Beta=3.18，95%CI=1.06-5.31，P=0.005）。在血液中，FEV/FVC<LLN 与更大的 GrimAge 残差相关（Beta=1.74，95%CI=0.37-3.24，P=0.019）。FEV 下降与血液中的 GrimAge 残差呈负相关（r=-0.13，P=0.012）。在 6 年内肺功能正常但随后出现 FEV/FVC<0.70 的 PLWH，其基线时的 GrimAge 残差更高（Beta=2.33，95%CI=0.23-4.44，P=0.031）。
GrimAge 可能反映了与晚期气流阻塞相关的肺和系统表观遗传变化，并可能有助于识别发生 COPD 的风险较高的 PLWH。
加拿大卫生研究院和不列颠哥伦比亚省肺协会。START 子研究由 NIH 资助：UM1-AI068641、UM1-AI120197 和 RO1HL096453。
