METHODS A case-control study is presented. OBJECTIVE To investigate the association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. BACKGROUND Studies have shown that idiopathic scoliosis is related to genetic factors, such as XbaI site polymorphism of the estrogen receptor alpha gene. To our knowledge, however, the relationship of estrogen receptor beta gene polymorphisms and the individual susceptibility to idiopathic scoliosis has not been studied. METHODS This study included 218 patients with AIS and 140 healthy controls. Height, menarche status, curve pattern, Cobb angle, and Risser sign in female patients were recorded. Blood samples were taken from each subject by venipuncture. Genomic DNA was extracted from peripheral blood leukocytes using standard phenol/chloroform extraction. PCR products from amplification of genomic DNA from all individuals were analyzed using denaturing high-performance liquid chromatography. Samples with aberrant HPLC profiles were sequenced in both the forward and the reverse directions on an ABI 3100 automated sequencer. The chi test was used to determine the significant difference in genotype distribution between patients with AIS and the controls. RESULTS The frequency of CC genotype of the exon ØK (in reality 5' UTR OK-1)was significantly higher in patients than that in controls (P < 0.05). The C alleles appeared to be overrepresented in patients compared with controls (P < 0.05). Furthermore, the frequencies of CC genotypes in female patients whose height was > or =160 cm and Cobb angle was > or =30 degrees were higher than those whose height was <160 cm and Cobb angle was <30 degrees (P < 0.05). CONCLUSION.: The sites of the exon ØK polymorphisms of estrogen receptor beta gene may be associated with a susceptibility of AIS. Furthermore, the sites of the exon ØK polymorphism may be associated with the height and the curve severity of patients.