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HIV与老年人中和年龄相关的克隆性造血风险增加有关
作者:小柯机器人 发布时间:2021/6/9 14:43:01

澳大利亚墨尔本大学Mark A. Dawson等研究人员发现,HIV与老年人中和年龄相关的克隆性造血风险增加有关。2021年6月7日,《自然—医学》杂志在线发表了这项成果。

研究人员表示,与未感染 HIV 的人相比,感染HIV的人患某些合并症的比率更高,尤其是心血管疾病和癌症。鉴于观察到与年龄相关的克隆性造血(CH)相关的体细胞突变与一般人群中的类似合并症有关,研究人员假设CH可能在HIV感染者中更为普遍。

为了回答这个问题,研究人员建立了一项前瞻性队列研究,即ARCHIVE研究(NCT04641013),其中在澳大利亚招募了220名年龄在55岁或以上的HIV阳性和226名HIV阴性参与者。收集人口统计学特征、临床数据和外周血以评估CH突变的存在并确定CH的潜在危险因素和临床后遗症。总共在446名参与者中的100 名(22.4%)中发现了135个CH突变。

CH在HIV阳性参与者中比HIV阴性参与者中更普遍(28.2% 对 16.8%,P=0.004),无论是总体上还是在所有年龄组中;HIV感染者患CH的调整优势比为2.16(95% 置信区间1.34–3.48,P=0.002)。最常见的突变基因是DNMT3A(47.4%)、TET2(20.0%)和 ASXL1(13.3%)。CH和HIV感染与血液参数和与炎症相关的生物标志物的增加独立相关。这些数据表明,在慢性感染和与HIV感染相关的炎症背景下,CH的出现具有选择性优势。 

附:英文原文

Title: HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults

Author: Nila J. Dharan, Paul Yeh, Mark Bloch, Miriam M. Yeung, David Baker, Jerick Guinto, Norman Roth, Sarah Ftouni, Katherine Ognenovska, Don Smith, Jennifer F. Hoy, Ian Woolley, Catherine Pell, David J. Templeton, Neil Fraser, Nectarios Rose, Jolie Hutchinson, Kathy Petoumenos, Sarah-Jane Dawson, Mark N. Polizzotto, Mark A. Dawson

Issue&Volume: 2021-06-07

Abstract: People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1,2,3,4,5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6,7,8,9,10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P=0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34–3.48, P=0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

DOI: 10.1038/s41591-021-01357-y

Source: https://www.nature.com/articles/s41591-021-01357-y

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex