Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Front Immunol. 2024 Aug 26;15:1403429. doi: 10.3389/fimmu.2024.1403429. eCollection 2024.
Currently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomization (MR) methodology to investigate the causal relationship between the two.
This study selected 110 single-nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome-wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalog and FINNGEN database, primarily analyzed using inverse variance weighting (IVW) and sensitivity analysis.
Through MR analysis, we identified 9 primary immunodeficiency-related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections.
This study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations are warranted to explore the specific mechanisms underlying these connections.
目前，原发性免疫缺陷相关基因与水痘-带状疱疹病毒再激活综合征之间因果关系的证据有限且不一致。因此，本研究采用孟德尔随机化（MR）方法来研究两者之间的因果关系。
本研究选择了 110 个原发性免疫缺陷相关基因的单核苷酸多态性（SNP）作为工具变量（IV）。原发性免疫缺陷相关基因的遗传相关性源自人类血浆蛋白水平和循环免疫细胞的全基因组关联研究（GWAS）数据。与水痘-带状疱疹病毒再激活综合征相关的基因数据来自 GWAS 目录和 FINNGEN 数据库，主要使用逆方差加权（IVW）和敏感性分析进行分析。
通过 MR 分析，我们确定了 9 个与带状疱疹及其随后的神经痛有因果关系的原发性免疫缺陷相关基因；确定了 20 个原发性免疫缺陷相关基因与三种血管病变（中风、脑动脉瘤、巨细胞动脉炎）之间的因果关系；揭示了 10 个原发性免疫缺陷相关基因与两种眼部疾病（视网膜病变、角膜炎）之间的因果关系；此外，三个原发性免疫缺陷相关基因分别与脑炎、颅神经麻痹和胃肠道感染有关。
本研究发现原发性免疫缺陷相关基因与水痘-带状疱疹病毒再激活综合征之间存在一定关联，但需要进一步研究来探讨这些关联的具体机制。
