Genomic polymorphisms of G-protein estrogen receptor 1 are associated with severity of adolescent idiopathic scoliosis

Abstract

Purpose: Adolescent idiopathic scoliosis (AIS) is reported to be associated with the two traditional estrogen receptor genes, ESR1 and ESR2. Yet, the novel estrogen receptor G protein-coupled estrogen receptor 1 (GPER) has not been studied. To investigate the association of GPER gene polymorphisms with the onset and deterioration of AIS, we performed a case-control study.

Methods: Clinical information was recorded, blood samples were taken and genomic DNA was extracted. After resequencing the gene in 45 cases and 45 controls who were randomly selected, 16 tag single nucleotide polymorphisms (SNPs) were selected. Then the association study was extended by an additional 344 patients and 293 controls with direct sequencing and a TaqMan-based genotyping assay. The chi-square test and logistic regression were used to analyse the genotypic and allelic association. One-way analysis of variance was used to compare the mean maximum Cobb angles and ages with different genotypes in the case-only data set.

Results: No association was observed between the polymorphisms of the GPER gene and susceptibility to AIS. However, heterozygotes in three SNPs of the gene (rs3808351, rs10269151 and rs426655s3) were related significantly with the curve severity in AIS patients (P = 0.004, 0.048 and 0.028, respectively).

Conclusions: Our results demonstrate that GPER gene polymorphisms are associated with the severity of curvature in AIS; deficits of GPER may contribute to the deterioration of spine deformity.

Fig. 1

LD pattern of the GPER gene from the 45 healthy subjects. There were four LD blocks in the 11 kb sequenced genomic region of the gene, which were calculated by the solid spine of the LD algorithm with a minor allele frequency ≥1%. The highlighted numbers stand for D′