Elevated UMOD methylation level in peripheral blood is associated with gout risk

Uromodulin (UMOD) encodes an uromodulin glycoprotein, and its mutation results in uromodulin glycoprotein dysfunction and the occurrence of gout. The aim of our study was to assess whether UMOD methylation could predict the risk of gout. A total of 89 sporadic gout cases and 103 age and gender-matched healthy controls were recruited in this study. UMOD methylation level was determined by quantitative methylation-specific PCR (qMSP) in peripheral blood, and the percentage of methylated reference (PMR) was described to represent the methylation level. Our results showed that UMOD methylation was significantly higher in gout cases than controls (median: 1.45 versus 0.75, P < 0.001). The area under curve (AUC) of UMOD methylation in gout was 0.764 (P = 2.90E-10) with a sensitivity of 65.2% and a specificity of 88.3%. UMOD methylation level was shown to be significantly correlated with the serum level of uric acid (UA) (r = −0.208, P = 0.035). Besides, the luciferase reporter assay showed that UMOD CpG island region was able to upregulate gene expression (fold change = 2, P = 0.004). In conclusion, UMOD methylation assessment might be used to predict the occurrence of gout.