title: Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations.
abstract: Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China. Electronic address: xu_jifeng@hotmail.com.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Guang-hai
authors.initials: GH
authors.lastname: Yang
authors.affiliation: Department of Cardiolopy, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Pan
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Shui-Jun
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Bin-Song
authors.initials: BS
authors.lastname: Qiu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Hong
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bi
authors.affiliation: Department of Cardiolopy, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, PR China. Electronic address: wangypzju@163.com.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012600:Scoliosis / Q000235:genetics*
chemical_list: C488660:ADGRG6 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Adolescent idiopathic scoliosis; Association; GPR126; Intronic SNPs