Deciphering the causal effect of metabolic syndrome and its components on pruritus: Evidence from Mendelian randomization study

Observational studies have indicated an association between metabolic syndrome (MetS) and pruritus. However, the causality between them remains unclear. This study aims to assess the causality of MetS and its components on pruritus. Genetic variation of MetS and its components were selected from the genome-wide association study as instrumental variables, with the inverse variance weighted method as the main analytical approach. Univariate and multivariate Mendelian randomization (MR) analyses were used to assess the causal effects of MetS and its components on pruritus. Sensitivity analyses were performed to ensure the results' robustness. Univariate MR analysis indicated no causal relationship between MetS and pruritus. Among the components of MetS, very low-density lipoprotein cholesterol (odds ratio [OR] = 1.447, 95% confidence interval [CI]: 1.164-1.799, P = .001), and type 2 diabetes (OR = 1.131, 95% CI: 1.009-1.266, P = .034) were associated with an increased risk of pruritus. Type 1 diabetes was also positively associated with pruritus (OR = 1.043, 95% CI: 1.008-1.080, P = .016). Conversely, body mass index (OR = 0.871, 95% CI: 0.764-0.992, P = .038), obesity (OR = 0.705, 95% CI: 0.543-0.915, P = .009), and high-density lipoprotein cholesterol (OR = 0.836, 95% CI: 0.709-0.986, P = .033) were negatively associated with the risk of pruritus. Multivariate MR analysis indicated that the above relationships remain unchanged after adjusting for confounding factors (All P < .05). This research demonstrates that MetS as a whole is not genetically causal for pruritus, whereas elevated very low-density lipoprotein cholesterol and diabetes significantly heighten the risk of pruritus. Early identification of these risk factors may be an effective strategy to reduce the occurrence of pruritus. These findings challenge the traditional view that MetS drives dermatological diseases, highlighting that the contribution of metabolic disturbances to pruritus is component-specific.