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端粒酶逆转录酶单核苷酸多态性 rs2736098 但不是 rs2736100 与接受 cART 的 HIV 感染患者的端粒长度相关。

TERT single nucleotide polymorphism rs2736098 but not rs2736100 is associated with telomere length in HIV-infected patients on cART.

机构信息

Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

Mol Biol Rep. 2024 Jan 18;51(1):147. doi: 10.1007/s11033-023-08967-4.

Abstract

BACKGROUND

Continuous application of "combination antiretroviral therapy" (cART) has transformed Human immunodeficiency virus (HIV) infection into a manageable chronic disease; however, due to lasting inflammation and cumulative toxicity, progressive pathophysiological changes do occur and potentially lead to accelerated aging, among others, contributing to telomere shortening. The single nucleotide polymorphisms (SNP) rs2736100 and rs2736098 are particularly important for human telomerase (TERT) gene expression. The objective of this study was to evaluate the effects of clinical parameters and single nucleotide polymorphisms in TERT (rs2736100 and rs2736098) on telomere length in HIV-infected patients.

METHODS AND RESULTS

This cross-sectional study included 176 patients diagnosed with HIV infection. Relative telomere length (RTL) was determined by real-time polymerase chain reaction (qPCR), whereas genotyping was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis (PCR-RFLP). The mean age of the patients (p = .904), time since HIV diagnosis (p = .220), therapy-related variables such as the cART regimen (0.761), and total cART duration (p = .096) did not significantly affect RTL. TERT rs2736100 genotype showed no association with RTL. However, TERT rs2736098 heterozygotes (GA) had significantly longer telomeres (P = .049) than both homozygotes (GG and AA).

CONCLUSIONS

Our findings support the fact that cellular aging in HIV-infected patients is influenced by the TERT rs2736098 polymorphism.

摘要

背景

连续应用“联合抗逆转录病毒疗法”(cART)将人类免疫缺陷病毒(HIV)感染转变为可管理的慢性疾病;然而,由于持续的炎症和累积的毒性,确实会发生进行性的病理生理变化,可能导致加速衰老等,导致端粒缩短。单核苷酸多态性(SNP)rs2736100 和 rs2736098 对人类端粒酶(TERT)基因表达尤为重要。本研究旨在评估临床参数和 TERT(rs2736100 和 rs2736098)中的单核苷酸多态性对 HIV 感染患者端粒长度的影响。

方法和结果

本横断面研究纳入了 176 例 HIV 感染患者。通过实时聚合酶链反应(qPCR)确定相对端粒长度(RTL),通过聚合酶链反应进行基因分型,然后通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)进行分析。患者的平均年龄(p=0.904)、HIV 诊断后的时间(p=0.220)、治疗相关变量,如 cART 方案(0.761)和总 cART 持续时间(p=0.096)均未显著影响 RTL。TERT rs2736100 基因型与 RTL 无相关性。然而,TERT rs2736098 杂合子(GA)的端粒明显长于纯合子(GG 和 AA)(P=0.049)。

结论

我们的研究结果支持 HIV 感染患者的细胞衰老受 TERT rs2736098 多态性影响的事实。

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