Despite the confirmation of the role for LBX1 gene variants in the development of AIS, the biological basis of LBX1 contribution to AIS remains mostly unknown.
We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay.
Although the LBX1 locus is so far the most successfully replicated locus in different AIS cohorts, these associations were replicated mainly in Asian populations, with few studies in Caucasian populations of European descent.
Our meta-analysis provides evidence that rs111090870, rs678741 and rs625039 polymorphisms near LBX1 gene are associated with AIS susceptibility in some populations.
In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10(-37)), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS.
We found rs11190870, downstream of LBX1 and previously associated with AIS in Asian populations, to be in modest linkage disequilibrium (LD) with rs11190878 (r(2) = 0.40, D' = 0.81).
Our results firmly establish the LBX1 region as the first major susceptibility locus for AIS in Asian and non-Hispanic white groups, and provide a platform for larger studies in additional ancestral groups.
The rs11190870 single nucleotide polymorphism in the 3'-flanking region of the LBX1 gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS).