Abstract
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.
Highlights
Gout is one of the oldest described rheumatic diseases
High-density lipoprotein (HDL) cholesterol concentration was measured by enzymatic colorimetric methods with commercially available kits, and low-density lipoprotein (LDL) cholesterol concentration was measured by homogeneous assay[24]
Significantly higher levels of ALT, uric acid (UA), Glu, cholesterol, TG and white blood cell (WBC) were found in the gout cases than controls
Summary
Gout is one of the oldest described rheumatic diseases. It affects 1–2% of the global population[1]. There are many risk factors for the development of gout, including hyperuricaemia, dietary factors, alcohol consumption, metabolic syndrome, hypertension, obesity, diuretic use, chronic renal disease, and genetic factors[3, 4]. Little research about the association between DNA methylation and the pathogenesis of gout has been reported. Previous study showed that gout was associated with UMOD gene mutations[12]. UMOD gene variants were associated with susceptibility to the risk of chronic kidney disease in several genome-wide association studies[13]. We measured UMOD methylation level in peripheral blood to explore its association with gout in Chinese Han male population
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