A germline mutation of the thyroid-stimulating hormone receptor (TSHR) gene has been reported to be associated with thyrotoxicosis and mitral valve prolapse syndrome (MVPS) in a Chinese family. The role of TSHR genetic variants in MVPS has not been well studied. This study investigated the possible relationship between the polymorphisms of codon 727 and 52 of the TSHR gene and MVPS among the Chinese population in Taiwan. We studied 100 patients with MVPS diagnosed by echocardiography and 100 ageand sex-matched normal control subjects. The polymorphisms of codon 727 and 52 of the TSHR gene were identified by polymerase chain reaction-based restriction analysis. There was no significant difference in either the genotype distribution or allelic frequencies between MVPS cases and controls for either TSHR gene D727E polymorphism ( = 0.51 and 0.45, respectively ) or P52T polymorphism (P = 0.60 and 0.31, respectively). The MVPS patients were divided into 2 subgroups: those with Graves' disease, and those without the thyroid disorder, and there were no statistical differences from the controls for both the TSHR gene D727E and P52T polymorphisms. Further categorization of the MVPS patients into mild and severe subgroups also revealed no statistical difference from controls for either the TSHR gene D727E or P52T polymorphisms. These findings suggest that the codon 727 and 52 polymorphisms of the TSHR gene are not the suitable genetic markers of MVPS in Taiwan Chinese.