Study Design. A case-control association study was conducted to investigate the genetic etiology for congenital scoliosis (CS) in a Chinese Han population.
Objective. To identify whether TBX6 polymorphisms are associated with susceptibility to CS in a Chinese Han population.
Summary of Background Data. CS is a 3-dimensional deformity of the spine, resulting from defection of normal vertebral development. Although there are many types of defects observed in CS, all result from abnormal formation and segmentation of the vertebral precursors, called somites. Developmental studies in animal models have identified many genes regulating somite formation and segmentation. T-box factor, TBX6, is a prerequisite for somite segmentation in vertebrates. In mouse TBX6 knockouts, the phenotypes are similar with that of some human birth defects, such as CS, raises the possibility that TBX6 gene may be a potential susceptibility gene for CS, so we investigated the relations between TBX6 polymorphisms and CS.
Methods. Two known single-nucleotide polymorphisms (SNPs) of TBX6 gene were genotyped among 254 Chinese Han subjects (127 CS patients and 127 controls with matched sex and age) by GenomeLab SNPstream genotyping system. The 2 markers (the only tagging SNP and a functional SNP) with minor allele frequency above 5% were analyzed by the allelic and genotypic association analysis, the genotype-phenotype (CS patients were divided into type I 31 cases [failure of formation], type II 46 cases [a failure of segmentation], and type III 50 cases [mixed defects]) association analysis, and the haplotype analysis.
Results. The single SNP analysis showed allele frequency of rs2289292 (exon 8, the only tagging SNP) and rs3809624 (5′ untranslated region) demonstrated significant difference between CS cases and controls (P = 0.017 and P = 0.033). No SNP was found to be correlated with clinical phenotype. Moreover, the 2 makers (rs2289292 and rs3809624) in TBX6 gene were found to be in strong linkage disequilibrium (D' = 1.0; γ2 = 0.984; 95% confidence interval, 0.96–1.0; LOD = 57.48) in the controls. Both global haplotype analysis and individual haplotype analysis showed that the haplotype of SNP1/SNP2 showed significant association with the disease (P = 0.017), G-A haplotype was more frequently observed in controls than in cases (odds ratio, 0.71; 95% confidence interval, 0.51–0.99).
Conclusion. This is the first report on SNPs of TBX6 gene in CS that suggests genetic variants of TBX6 gene is associated with CS and may play an important role in mediating susceptibility to developing CS in the Chinese Han population.