title: A replication study for association of 5 single nucleotide polymorphisms with curve progression of adolescent idiopathic scoliosis in Japanese patients.
abstract: METHODS
  A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS).
  
  
  OBJECTIVE
  To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS.
  
  
  BACKGROUND
  AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them.
  
  
  METHODS
  We recruited 2117 patients with AIS with a Cobb angle of 10° or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40° or greater were included in the progression group, and those whose scoliotic curves were less than 30° and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype.
  
  
  RESULTS
  We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs.
  
  
  CONCLUSIONS
  The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.
authors.affiliation: Laboratory of Bone and Joint Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Kou
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakajima
authors.forename: Katsuki
authors.initials: K
authors.lastname: Kono
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawakami
authors.forename: Koki
authors.initials: K
authors.lastname: Uno
authors.forename: Manabu
authors.initials: M
authors.lastname: Ito
authors.forename: Shohei
authors.initials: S
authors.lastname: Minami
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Yanagida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Taneichi
authors.forename: Ikuho
authors.initials: I
authors.lastname: Yonezawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Teppei
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hideki
authors.initials: H
authors.lastname: Sudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kotani
authors.forename: Kota
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020933:Neurotrophin 3 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D011960:Receptors, Estrogen / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D012720:Severity of Illness Index; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
chemical_list: C109584:GPER1 protein, human; D020933:Neurotrophin 3; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2