Association Between Estrogen Receptor Gene Polymorphism and Idiopathic Scoliosis

Chiba University, Chiba, Japan

PURPOSE:
The study of disease association can reveal the identity of one of the polygenes contributing to a multifactorial disorder. Many studies have suggested that idiopathic scoliosis is a familial condition of multifactorial inheritance and that curve progression is also related to genetic factors, such as skeletal growth and menarche. Recently association between estrogen receptor (ER) gene and skeletal growth was reported. The purpose of this study was to determine whether DNA polymorphisms of the ER gene are related to the pathogenesis of adolescent idiopathic scoliosis.

PATIENTS AND METHODS:
Two-hundred and seventy-five girls with adolescent idiopathic scoliosis were examined. 120 patients had brace treatment, 30 patients were operated on, while 125 patients did not show curve progression. Individual DNA was extracted from peripheral lymphocytes, and the ER gene, which contains the Pvu II and Xba I sites, was amplified by polymerase chain reaction (PCR). The PCR products were digested with Pvu II and Xba I enzymes, and genotypes were determined by agarose gel electrophoresis. DNA polymorphisms were coded as Pp (Pvu II) and Xx (Xba I), where the uppercase letter indicates the absence of the site, while the lower letter its presence.

RESULTS:
Xba I site polymorphism was associated with curve severity. The mean Cobb's angle of patients with genotype XX was 34.1 degrees, and that of those with genotype Xx was 33.3 degrees, while that of patients with genotype xx was 28.9 degrees (p = 0.01). Except for the patients treated with brace, the mean Cobb's angle of patients with genotype XX was 35.5 degrees, and that of those with genotype Xx was 34.3 degrees, while that of patients with genotype xx was 24.1 degrees (p<0.01). Furthermore, 17.6% of the patients with genotype XX and 18.9% of those with genotype Xx had to be operated on, while only 6.0% of the patients with genotype xx required surgical treatment. (p<0.01). Pvu II site polymorphism was not associated with curve severity.

CONCLUSIONS:
It was suggested that ER gene polymorphism was related to the pathogenesis of idiopathic scoliosis. DNA analysis may predict curve progression.