TLR2、TLR4 和 TLR9 基因多态性对人类免疫缺陷病毒-1 疾病进展的影响。

Influence of genetic variability in toll-like receptors (TLR 2, TLR 4, and TLR 9) on human immunodeficiency virus-1 disease progression.

机构信息

School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh; Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.

Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Int J Mycobacteriol. 2023 Jan-Mar;12(1):10-16. doi: 10.4103/ijmy.ijmy_190_22.

DOI:10.4103/ijmy.ijmy_190_22

PMID:36926756

Abstract

BACKGROUND

It has been demonstrated that toll-like receptors (TLR2), TLR4, and TLR9 which were initially known for recognizing bacterial products are involved in the detection of viral components. It was planned to undertake a prospective longitudinal study among ethnically homogeneous antiretroviral treatment and antitubercular treatment naïve human immunodeficiency virus (HIV)-positive patients representing the north Indian population. The aim of the study was to investigate the influence of TLR2, TLR4, and TLR9 polymorphism in HIV disease progression.

METHODS

The present study was designed to investigate genetic polymorphism in TLRs (TLR2, TLR4, and TLR9) among HIV-infected patients with and without TB coinfection. The study population consisted of two groups: (i) HIV-positive patients without TB infection and disease (n = 223, HIV-positive patients); (ii) HIV-positive patients with latent tuberculosis infection (LTBI) (n = 150, HIV-positive LTBI patients). These participants were of either gender between 18 and 60 years of age and treatment naïve for both TB and HIV. HIV-positive and HIV-positive LTBI patients were longitudinally followed up for t2 years to study HIV disease progression.

RESULTS

On comparing TLR2 and TLR4 allelic and genotypic frequencies between 306 HIV-positive patients (no TB/AIDS) and 47 HIV-positive patients progressed to active TB/AIDS, no significant difference was observed between the two groups. The frequency of "A" allele in TLR9 was found to be significantly increased in 47 HIV-positive patients who progressed to active TB/AIDS (61.7%) as compared to 42.16% in 306 HIV-positive patients (no TB/AIDS), (P < 0.001). Furthermore, a significantly increased frequency of "AA" genotype in TLR9 was observed in 47 HIV-positive patients progressed to active TB/AIDS (55.32%) as compared to 20.26% in HIV-positive patients (no TB/AIDS).

CONCLUSION

Findings of the present study revealed that genetic variability in TLR9 may influence HIV disease progression. The AA genotype in TLR9 may be associated with progression to TB/AIDS for 2 years in HIV-positive patients.

摘要

背景

最初被认为识别细菌产物的 toll 样受体 (TLR2)、TLR4 和 TLR9 已被证明参与了病毒成分的检测。本研究计划在代表北印度人群的、未经抗逆转录病毒治疗和抗结核治疗的、种族单一的 HIV 阳性患者中进行一项前瞻性纵向研究。该研究旨在探讨 TLR2、TLR4 和 TLR9 多态性对 HIV 疾病进展的影响。

方法

本研究旨在调查 HIV 感染患者中 TLR（TLR2、TLR4 和 TLR9）基因多态性与 TB 合并感染的关系。研究人群分为两组：（i）无 TB 感染和疾病的 HIV 阳性患者（n=223，HIV 阳性患者）；（ii）潜伏性结核感染的 HIV 阳性患者（n=150，HIV 阳性 LTBI 患者）。这些参与者均为 18-60 岁之间的男性和女性，且均未接受过针对 TB 和 HIV 的治疗。对 HIV 阳性和 HIV 阳性 LTBI 患者进行了长达 2 年的纵向随访，以研究 HIV 疾病进展情况。

结果

在比较 306 名无 TB/AIDS 的 HIV 阳性患者和 47 名进展为活动性 TB/AIDS 的 HIV 阳性患者的 TLR2 和 TLR4 等位基因和基因型频率时，两组之间未观察到显著差异。在进展为活动性 TB/AIDS 的 47 名 HIV 阳性患者中，TLR9 的“A”等位基因频率明显高于无 TB/AIDS 的 306 名 HIV 阳性患者（61.7%对 42.16%），（P < 0.001）。此外，在进展为活动性 TB/AIDS 的 47 名 HIV 阳性患者中，TLR9 的“AA”基因型频率也明显高于无 TB/AIDS 的 HIV 阳性患者（55.32%对 20.26%）。