Genetically predicted amino acids related to neural regulation mediate the association between diabetes mellitus and postherpetic neuralgia: a Mendelian randomization study

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BACKGROUND: Postherpetic neuralgia (PHN) and diabetes mellitus frequently coexist in clinical settings; however, the causal relationship between them remains unclear. Moreover, the potential mediating role of amino acids related to neural regulation in this association has not been fully explored yet. METHODS: Univariable Mendelian randomized (UVMR) was utilized to examine the causal relationship between various subtypes of diabetes mellitus and PHN, with the inverse variance weighted method as the main approach. Multivariable MR (MVMR) was conducted to assess the direct effect of diabetes mellitus, accounting for waist circumference, diabetic neuropathy/ulcers, and depression. Moreover, a two-step MR analysis was employed to investigate the mediating role of neurotransmitter-related amino acids in the association between diabetes mellitus and PHN. RESULTS: A significant statistical correlation was found between type 2 diabetes mellitus (T2DM) and PHN (odds ratio, OR: 1.23, 95% confidence interval, CI: 1.01-1.49, P = 0.036), while in type 1 diabetes mellitus or pregnancy diabetes mellitus, no evidence of the association with PHN was observed. MVMR analyses demonstrated that the effect of T2DM on PHN remained significant after adjusting for waist circumference, diabetic neuropathy/ulcers, and depression. Further mediation analysis revealed that phenylalanine accounted for 49.2% (95% CI: 22.7- 75.6%) of the total effect of T2DM on PHN. CONCLUSION: The current study suggested that T2DM was associated with an increased risk of PHN, with phenylalanine playing a mediating role. These findings provided valuable insights for the screening and prevention of PHN in clinical practice.

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