Barrios-Navas Alejandro, Nguyen Thanh Long, Gallo Juan Esteban, Mariño-Ramírez Leonardo, Soto José María Satizabal, Sánchez Adalberto, Jordan I King, Valderrama-Aguirre Augusto
Grupo Instituto de Investigaciones Biomédicas, Departamento de Ciencias Biológicas, Facultad de Ciencias, Universidad de Los Andes, Bogotá, DC, Colombia.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
Infect Genet Evol. 2024 Nov;125:105680. doi: 10.1016/j.meegid.2024.105680. Epub 2024 Oct 5.
AIDS remains a significant global health challenge since its emergence in 1981, with millions of deaths and new cases every year. The CCR5 ∆32 genetic deletion confers immunity to HIV infection by altering a cell membrane protein crucial for viral entry. Stem cell transplants from homozygous carriers of this mutation to HIV-infected individuals have resulted in viral load reduction and disease remission, suggesting a potential therapeutic avenue. This study aims to investigate the relationship between genetic ancestry and the frequency of the CCR5 ∆32 mutation in Colombian populations, exploring the feasibility of targeted donor searches based on ancestry composition. Utilizing genomic data from the CÓDIGO-Colombia consortium, comprising 532 individuals, the study assessed the presence of the CCR5 ∆32 mutation and examined if the population was on Hardy-Weinberg equilibrium. Individuals were stratified into clusters based on African, American, and European ancestry percentages, with logistic regression analysis performed to evaluate the association between ancestry and mutation frequency. Additionally, global genomic databases were utilized to visualize the worldwide distribution of the mutation. The findings revealed a significant positive association between European ancestry and the CCR5 ∆32 mutation frequency, underscoring its relevance in donor selection. African and American ancestry showed negative but non-significant associations with CCR5 ∆32 frequency, which may be attributed to the study's limitations. These results emphasize the potential importance of considering ancestry in donor selection strategies, reveal the scarcity of potential donors in Colombia, and underscore the need to consider donors from other populations with mainly European ancestry if the CCR5 ∆32 stem cell transplant becomes a routine treatment for HIV/AIDS in Colombia.
自1981年出现以来,艾滋病仍然是一项重大的全球卫生挑战,每年有数百万例死亡和新发病例。CCR5 ∆32基因缺失通过改变一种对病毒进入至关重要的细胞膜蛋白,赋予对HIV感染的免疫力。将这种突变的纯合携带者的干细胞移植到HIV感染个体中,已导致病毒载量降低和疾病缓解,这表明了一种潜在的治疗途径。本研究旨在调查哥伦比亚人群中遗传血统与CCR5 ∆32突变频率之间的关系,探索基于血统构成进行靶向供体搜索的可行性。利用来自CÓDIGO - 哥伦比亚联盟的532名个体的基因组数据,该研究评估了CCR5 ∆32突变的存在情况,并检查该人群是否处于哈迪 - 温伯格平衡。个体根据非洲、美洲和欧洲血统百分比分层,进行逻辑回归分析以评估血统与突变频率之间的关联。此外,利用全球基因组数据库来可视化该突变在全球的分布。研究结果显示欧洲血统与CCR5 ∆32突变频率之间存在显著正相关,突出了其在供体选择中的相关性。非洲和美洲血统与CCR5 ∆32频率呈负相关但不显著,这可能归因于该研究的局限性。这些结果强调了在供体选择策略中考虑血统的潜在重要性,揭示了哥伦比亚潜在供体的稀缺性,并强调如果CCR5 ∆32干细胞移植成为哥伦比亚HIV/AIDS的常规治疗方法,需要考虑来自其他主要为欧洲血统人群的供体。