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Abstract: Objecitve To identify the different serum proteins expressed in patients with Keshan disease (KD). Methods Two -dimensional gel electrophoresis (2-DE) was performed with serum samples from the patients with chronic KD and healthy controls to separate serum proteins. The gels were stained by sliver and scanned by Umax scanner. The data were analyzed by ImageMaster 2D software. KD related proteins were identified through searching the ExPASy-SWISS-2DPAGE database. Results Stable two-dimensional gel electrophoresis maps were established for serum samples of KD patients and healthy controls. A total of 808 and 814 protein spots were observed in KD patients and healthy controls, respectively. The two maps had 96.5475% identical protein spots and 44 differentially expressed protein spots. Eleven protein spots were expressed exclusively in KD patients and 12 protein spots only appeared in healthy controls. About 21 proteins were expressed in both groups but varied in quantities (14 proteins were over-expressed by more than 3 times and 7 proteins were under-expressed by more than 3 times in KD patients, P<0.01). Among the 353 protein spots matched with the ExPASy-SWISS-2DPAGE databank, No.1177 protein appeared in the KD patient was found to have the closest match with P02774 2-D0004T6 known as vitamin D binding protein (VDBP). Conclusion There is a significant difference in serum protein expression between KD patients and normal people. VDBP might play a role in cardiac muscle damage via inflammatory immune reactions.