Yang Xueying, Li Dairui, Chen Yuqing, Zhang Xuerong, Zhao Qiong
Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People's Republic of China.
Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
J Pain Res. 2025 Mar 21;18:1479-1489. doi: 10.2147/JPR.S501674. eCollection 2025.
Diabetes mellitus (DM), herpes zoster (HZ) and its sequelae, post-herpetic neuralgia (PHN), are common in elderly individuals. Previous observational studies have shown that the prevalence of HZ and PHN in conjunction with DM is increasing. Nonetheless, few studies have investigated the causal relationships between DM and the risk of HZ and PHN.
A two-sample Mendelian randomization (TSMR) analysis was conducted on genome-wide association study (GWAS) data. We obtained four separate datasets for DM: type 1 diabetes (T1D), type 2 diabetes (T2D), mother diabetes mellitus (mother-DM) and father diabetes mellitus (father-DM), and two independent datasets for HZ and anti-varicella-zoster virus IgG (VZV-IgG), a single GWAS for PHN. The inverse variance weighted (IVW), MR‒Egger, weighted median and weighted mode analyses were used to estimate the causality.
Genetically predicted T1D increased the level of VZV-IgG (IVW: OR=1.011, 95% CI 1.006-1.016, =8.44×10). T2D (IVW: OR=1.313; 95% CI 1.043-1.655, =0.041), mother-DM (IVW: OR=7.909; 95% CI 1.232-50.777, =0.039), and father-DM (IVW: OR=11.798; 95% CI 2.051-67.874, =0.023) increased the risk of PHN. No reverse causality was found between HZ, PHN, and DM.
Our research reveals a causal link between genetically determined T1D and increased VZV-IgG levels. Additionally, genetically predicted T2D and a family history of DM increase the risk of PHN. These discoveries deepen our comprehension of the underlying causes of HZ and PHN.
糖尿病（DM）、带状疱疹（HZ）及其后遗症带状疱疹后神经痛（PHN）在老年人中很常见。先前的观察性研究表明，糖尿病合并HZ和PHN的患病率正在上升。尽管如此，很少有研究调查DM与HZ和PHN风险之间的因果关系。
对全基因组关联研究（GWAS）数据进行两样本孟德尔随机化（TSMR）分析。我们获得了四个独立的糖尿病数据集：1型糖尿病（T1D）、2型糖尿病（T2D）、母亲糖尿病（母亲-DM）和父亲糖尿病（父亲-DM），以及两个独立的HZ和抗水痘带状疱疹病毒IgG（VZV-IgG）数据集，一个用于PHN的GWAS。采用逆方差加权（IVW）、MR-Egger、加权中位数和加权模式分析来估计因果关系。
遗传预测的T1D增加了VZV-IgG水平（IVW：OR = 1.011，95% CI 1.006 - 1.016，P = 8.44×10）。T2D（IVW：OR = 1.313；95% CI 1.043 - 1.655，P = 0.041）、母亲-DM（IVW：OR = 7.909；95% CI 1.232 - 50.777，P = 0.039）和父亲-DM（IVW：OR = 11.798；95% CI 2.051 - 67.874，P = 0.023）增加了PHN的风险。在HZ、PHN和DM之间未发现反向因果关系。
我们的研究揭示了遗传决定的T1D与VZV-IgG水平升高之间的因果联系。此外，遗传预测的T2D和糖尿病家族史会增加PHN的风险。这些发现加深了我们对HZ和PHN潜在病因的理解。
