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.

Genetics and pathogenesis of idiopathic scoliosis

“…This finding has been replicated in a small Chinese candidate gene study [62]. A knockdown of GPR126 in zebrafish caused delayed ossification of the developing spine [61].…”

Genetic Markers for Adolescent Idiopathic Scoliosis on Chromosome 19p13.3 among Saudi Arabian Girls

“…Our study was performed in patients who were unrelated, and we found a risk for one marker. Xu et al [20] recently reported a case-control study that genotyped twenty SNPs of the GPR126 gene in unrelated AIS patients. They further added 10 exonic SNPs and 10 intronic polymorphisms in patients and compared them to those in controls, finding strong evidence in 30% of SNPs studied.…”

Genetic polymorphisms of GPR126 are functionally associated with PUMC classifications of adolescent idiopathic scoliosis in a Northern Han population

“…rs7774095, an intronic SNP of GPR126 , was first reported to be associated with AIS in a Japanese population in 2013 . Other studies in southern Chinese populations replicated the association of this locus . However, there was no clear functional evidence provided for this conclusion.…”

“…Subsequently, Xu et al . found this locus and two other loci (rs7774095 and rs7755109) in 352 southern Chinese cases and 149 controls. Recently, Qin et al .…”

“…Kou et al [8] identified rs6570507 as a susceptibility locus with AIS in 1,819 Japanese cases and 25,939 controls and found that the developing spine of a gpr126 knockdown zebrafish model had delayed ossification. Subsequently, Xu et al [15] found this locus and two other loci (rs7774095 and rs7755109) in 352 southern Chinese cases and 149 controls. Recently, Qin et al [16] found another functional locus (rs9403380) that regulates GPR126 expression in the paraspinal muscles of southern Chinese AIS patients.…”