Exploring the Link Between Diabetes, Herpes Zoster, and Post-Herpetic Neuralgia: Insights From Mendelian Randomization

Xueying Yang,1 Dairui Li,2 Yuqing Chen,1 Xuerong Zhang,1 Qiong Zhao1 1Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence : Qiong Zhao; Xuerong ZhangDepartment of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel +86-177-2425-0727; +86-137-2804-1776, Email [email protected]; [email protected]: 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.Methods: 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.Results: Genetically predicted T1D increased the level of VZV-IgG (IVW: OR=1.011, 95% CI 1.006– 1.016, P−FDR=8.44× 10− 6). T2D (IVW: OR=1.313; 95% CI 1.043– 1.655, P−FDR=0.041), mother-DM (IVW: OR=7.909; 95% CI 1.232– 50.777, P−FDR=0.039), and father-DM (IVW: OR=11.798; 95% CI 2.051– 67.874, P−FDR=0.023) increased the risk of PHN. No reverse causality was found between HZ, PHN, and DM.Conclusion: 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.Keywords: diabetes mellitus, herpes zoster, post-herpetic neuralgia, two-sample Mendelian randomization