OBJECTIVES: Glutathione peroxidase 1 (GPx1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides gene and the susceptibility of Kashin-Beck disease (KBD) in a Chinese population. Meanwhile, we detected the mRNA expression of GPx1 in blood and cartilage tissues between KBD and controls in order to analyze the transcriptional activity of GPx1 and explore molecular mechanism of KBD. METHODS: The GPx1 Pro198Leu genotype was determined in 161 KBD cases and 312 control individuals  with polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). The mRNA expression level of GPx1 was detected by Real-time PCR. RESULTS: The genotypic and allelic frequency of GPX1 were different statistically between KBD patients and healthy controls (P=0.016, 0.043, respectively). We found an overall protective effect of the Pro/Pro genotype on the risk of KBD. Carriers of Pro/Leu and Leu/Leu had an increased risk of KBD compared with homozygous wild-type (Pro/Pro) individuals (OR, 1.781; 95% CI, 1.127-2.814; P = 0.016). The results of Real-time PCR showed a significant difference of mRNA level of GPx1 in whole blood between the two groups (P=0.026), and expression of GPx1 mRNA in KBD patients decreased significantly coampared with controls. However, no significant difference was observed in cartilage tissues (P=0.162). CONCLUSIONS: The study suggested that the 198Pro/Leu polymorphism of GPx1 gene might be a genetic risk factor for KBD in the Chinese population. These results also indicated that this polymorphism at the GPx1 locus was a common event in KBD development and that  expression of GPx1 mRNA in KBD patients decreased significantly compared with controls might be involved in the pathogenesis of KBD. ^*This research is supported by National Natural Science Foundation of China (No. 30671820, 81172610).