Discovery and exploration of adaptive immune response-related drug targets in diabetic retinopathy by Mendelian randomization

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-02-01 DOI:10.1016/j.diabres.2025.111987

Ning Gao, Jingming Li, Ting Wei, Qiaochu Cheng, Shan Gao, Yaguang Hu

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引用次数: 0

Abstract

Background

Persistent diabetes raises diabetic retinopathy (DR) risk, and management is challenging. Integrating transcriptomics and MR, this study provides a current reference for the clinical treatment of DR by identifying potential drug targets in adaptive immune response-associated genes (AIR-RGs).

Methods

The GSE102485 dataset about AIR-RGs and DR was downloaded from a public database. Initially, the MR and Steiger test identified AIR-related candidate genes with causal associations to DR. Bayesian co-localization analysis pinpointed DR drug targets, followed by phenotype scanning for side effects. Functional enrichment and immune infiltration analyses elucidated target mechanisms in DR.

Results

Identified 27 AIR-RGs associated with DR, with TRAV23DV6 (OR = 1.367, 95 % CI = 1.005–1.859, p = 0.0046) as a risk factor. Co-localization analysis confirmed TRAV23DV6′s potential as a DR drug target. Phenotype scanning linked TRAV23DV6 to hepatocellular carcinoma, thromboembolism, and pyelonephritis, indicating potential side effects. TRAV23DV6 engages in adaptive immunity, autophagy, and antigen binding. DR involves infiltration of 22 immune cell types and activation of 16 immune functions related to TCR, BCR pathways, and TNF family. Correlation analysis shows high TRAV23DV6 expression, immune cell infiltration, and function activation may exacerbate DR.

Conclusion

TRAV23DV6 has been identified as a potential drug target for DR, offering a new perspective for the treatment of this condition.

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孟德尔随机化方法发现和探索糖尿病视网膜病变中与适应性免疫反应相关的药物靶点。

背景：持续性糖尿病增加糖尿病视网膜病变（DR）的风险，治疗具有挑战性。本研究结合转录组学和MR，通过识别适应性免疫反应相关基因（AIR-RGs）中的潜在药物靶点，为DR的临床治疗提供当前参考。方法：从公共数据库下载GSE102485 AIR-RGs和DR数据集。最初，MR和Steiger测试确定了与DR有因果关系的air相关候选基因。贝叶斯共定位分析确定了DR药物靶点，随后进行了表型扫描以寻找副作用。结果：鉴定出27个与DR相关的AIR-RGs，其中TRAV23DV6为危险因子（OR = 1.367,95 % CI = 1.005-1.859,p = 0.0046）。共定位分析证实了TRAV23DV6作为DR药物靶点的潜力。表型扫描将TRAV23DV6与肝细胞癌、血栓栓塞和肾盂肾炎联系起来，表明其潜在的副作用。TRAV23DV6参与适应性免疫、自噬和抗原结合。DR涉及22种免疫细胞类型的浸润和与TCR、BCR通路和TNF家族相关的16种免疫功能的激活。相关性分析显示，TRAV23DV6高表达、免疫细胞浸润和功能激活可能加重DR。结论：TRAV23DV6已被确定为DR的潜在药物靶点，为DR的治疗提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.