Estrogen receptor 2 gene polymorphism in idiopathic scoliosis

Abstract

Study Design. A genetic association study of estrogen receptor 2 gene ( ESR2 ) polymorphisms in idiopathic scoliosis (IS). Objective. To investigate association of the ESR2 polymorphisms with either predisposition to or progression of IS in Central European population. Summary of Background Data. In ESR2 the rs1256120 polymorphism was described to be associated with predisposition to and severity of IS in Chinese population. This observation has not been confi rmed in Japanese population. The ESR2 rs4986938 and rs1256049 polymorphisms were described to present association with breast cancer, rheumatoid arthritis, and bone mineral density, however the association with IS has not been evaluated. Methods. Case-control study of 248 females with IS and 243 healthy females was performed. Three single-nucleotide polymorphisms were studied using polymerase chain reaction-restriction fragments length polymorphism technique with the restriction enzymes: Alw NI (C/T rs1256120), Alu I (A/G rs4986938), and Rsa I (A/G rs1256049). The patients' medical history was evaluated, Cobb angle was measured and surgery rate established. The patients were analyzed in 3 subgroups according to curve progression velocity. Results. Neither the genotypes nor alleles distribution showed signifi cant differences between patients with IS and healthy controls. There was no signifi cant difference in genotype or allele frequency. In the Alu I site polymorphism a signifi cant difference in mean Cobb angle between genotypes was found: (AA, 31.9 ° ± 14.2 ° ; AG, 43.2 ° ± 17.8 ° ; and GG, 38.9 ° ± 19.0 ° ), P = 0.002. There was signifi cant difference in genotype distribution between patients with moderate ( < 40 ° ) versus severe ( ≥ 40 ° ) scoliosis, P = 0.0011; the minorallele frequency (AA) in recessive model of penetration was overrepresented in patients with Cobb angle below 40 ° , P = 0.0075, odds ratio = 3.65. Conclusion. No association between ESR2 polymorphism and predisposition to IS was found in Caucasan females. None of the previously reported associations of Alw NI site polymorphism could be confi rmed. ESR2 Alu I site polymorphism may be associated with curve severity.