Open AccessA Genetic Variant in GPR126 Causing a Decreased Inclusion of Exon 6 Is Associated with Cartilage Development in Adolescent Idiopathic Scoliosis Population
Author(s) -
Enjie Xu,
Wang Shao,
Heng Jiang,
Tao Lin,
Rui Gao,
Xuhui Zhou
Publication year - 2019
Publication title -
biomed research international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 126
eISSN - 2314-6141
pISSN - 2314-6133
DOI - 10.1155/2019/4678969
Subject(s) - exon , single nucleotide polymorphism , population , biology , medicine , genetics , gene , genotype , environmental health
Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity disease in adolescents but its etiology and pathogenesis are still unclear. The current study aims to identify the relationship between single nucleotide polymorphisms (SNPs) of G protein-coupled receptor 126 (GPR126) gene and AIS predisposition. GPR126 contains 26 exons and alternative splicing of exon 6 and exon 25 produces 4 protein-coding transcripts. We genotyped SNPs of GPR126 gene around exon 6 and exon 25 in 131 Chinese AIS patients and 132 healthy controls and provided evidence that SNP rs41289839 G>A is strongly associated with AIS susceptibility. Linkage disequilibrium analysis suggests that rs41289839 and other AIS-related SNPs were in strong LD. Next, we demonstrated that rs41289839 G>A inhibits the inclusion of exon 6 during alternative splicing, resulting in a decreased expression level of exon 6-included transcript (GPR126-exon6 in ) relative to the exon 6 excluded transcript (GPR126-exon6 ex ) by minigene assay. Chondrogenic differentiation experiment showed that GPR126-exon6 in has a high expression level relative to GPR126-exon6 ex during chondrogenic differentiation of hMSCs. Our findings indicate that newly discovered SNP is related to cartilage development and may provide valuable insights into the etiology and pathogenesis of adolescent idiopathic scoliosis.