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. 2024 Jan 20;29(1):66.
doi: 10.1186/s40001-024-01635-8.

SOX9 gene shows association with adolescent idiopathic scoliosis predisposition in Northwest Indians

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SOX9 gene shows association with adolescent idiopathic scoliosis predisposition in Northwest Indians

Hemender Singh et al. Eur J Med Res. .

Abstract

Background: Adolescent idiopathic scoliosis (AIS) is a common structural deformity of the spine affecting adolescent individuals globally. The disorder is polygenic and is accompanied by the association of various genetic loci. Genetic studies in Chinese and Japanese populations have shown the association of genetic variants of SOX9 with AIS curve severity. However, no genetic study evaluating the association of SRY-Box Transcription Factor 9 (SOX9) variants with AIS predisposition has been conducted in any Indian population. Thus, we aimed to investigate the association of the genetic variants of the SOX9 along with 0.88 Mb upstream region with AIS susceptibility in the population of Northwest India.

Methods: In total, 113 AIS cases and 500 non-AIS controls were recruited from the population of Northwest India in the study and screened for 155 genetic variants across the SOX9 gene and 0.88 Mb upstream region of the gene using Global Screening Array-24 v3.0 chip (Illumina). The statistical significance of the Bonferroni threshold was set at 0.000322.

Result: The results showed the association of 11 newly identified variants; rs9302936, rs7210997, rs77736349, rs12940821, rs9302937, rs77447012, rs8071904, rs74898711, rs9900249, rs2430514, and rs1042667 with the AIS susceptibility in the studied population. Only one variant, rs2430514, was inversely associated with AIS in the population, while the ten variants were associated with the AIS risk. Moreover, 47 variants clustered in the gene desert region of the SOX9 gene were associated at a p-value ≤ 0.05.

Conclusion: The present study is the first to demonstrate the association of SOX9 enhancer locus variants with AIS in any South Asian Indian population. The results are interesting as rs1042667, a 3' untranslated region (UTR) variant in the exon 3 and upstream variants of the SOX9 gene, were associated with AIS susceptibility in the Northwest Indian population. This provides evidence that the variants in the enhancer region of SOX9 might regulate its gene expression, thus leading to AIS pathology and might act as an important gene for AIS susceptibility.

Keywords: Case–control; Genetic heterogeneity; High-throughput genotyping; SOX9; Scoliosis.

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Conflict of interest statement

All authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Regional association plot representing 135 variants that passed the quality test in the SOX9 and 0.88 Mb upstream of the gene

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References

    1. Khanshour AM, Kou I, Fan Y, Einarsdottir E, Makki N, Kidane YH, et al. Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci. Hum Mol Genet. 2018;27(22):3986–3998. doi: 10.1093/hmg/ddy306. - DOI - PMC - PubMed
    1. Kou I, Takahashi Y, Johnson TA, Takahashi A, Guo L, Dai J, et al. Genetic variants in GPR126 are associated with adolescent idiopathic scoliosis. Nat Genet. 2013;45(6):676–679. doi: 10.1038/ng.2639. - DOI - PubMed
    1. Londono D, Kou I, Johnson TA, Sharma S, Ogura Y, Tsunoda T, et al. A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. J Med Genet. 2014;51(6):401–406. doi: 10.1136/jmedgenet-2013-102067. - DOI - PubMed
    1. Miyake A, Kou I, Takahashi Y, Johnson TA, Ogura Y, Dai J, et al. Identification of a susceptibility locus for severe adolescent idiopathic scoliosis on chromosome 17q24.3. PLoS ONE. 2013;8(9):e72802. doi: 10.1371/journal.pone.0072802. - DOI - PMC - PubMed
    1. Ogura Y, Kou I, Miura S, Takahashi A, Xu L, Takeda K, et al. A functional SNP in BNC2 is associated with adolescent idiopathic scoliosis. Am J Hum Genet. 2015;97(2):337–342. doi: 10.1016/j.ajhg.2015.06.012. - DOI - PMC - PubMed

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