摘要
Background:The sonic hedgehog(SHH)pathway is an important signaling pathway for neural tube closure.GLI family zinc finger 2(GLI2)is the major activation mediator of the SHH pathway;however,no single-nucleotide polymorphisms(SNPs)in GLI2 have been reported to be associated with human neural tube defects(NTDs)to date.Here,we evaluated a mutation in GLI2 in the Han Chinese population.Methods:We used SNPscan to genotype rs3738880 in the GLI2 coding region.We then investigated the function of this gene by Western blotting and dual-luciferase assays.Results:In this study,we found that the GLI2 missense variant rs3738880 significantly increased the risk of NTDs in the Han Chinese population via association studies in a cohort of 254 patients and 277 controls from Shanxi Province(odds ratio[OR]=1.89,95%confidence interval[CI]=1.28-2.80,P=0.0012).Additional stratified analyses demonstrated that rs3738880 was significantly related to spina bifida(114 cases,OR=2.01,95%CI=1.19–3.38,P=0.0067).Functional analysis revealed that rs3738880 did not affect GLI2 protein stability and significantly increased SHH activity because of the introduction of a potential phosphorylation site in GLI2.Conclusion:rs3738880 was a risk factor for NTDs in the Han Chinese population.
基金
This work was supported by grants from the National Key Basic Research Program of China[2016YFC1000502 to H.Wang and X Yang]
the National Natural Science Foundation of China[81430005 to H Wang,81472050 to X Yang]
Open project of National Population and Family Planning Key Laboratory of Contraceptive drugs and Devices[2016KF04 for X Yang].
