The GLI2 Missense Variant rs3738880 Significantly Increases the Risk of Neural Tube Defects in the Han Chinese Population  

作　　者：Chen Shu-Xia Li Hui-Li Li Cai-Hua Zhang Ting Wang Hong-Yan Yang Xue-Yan 

机构地区：[1]State Key Laboratory of Genetic Engineering,MOE Key Laboratory of Contemporary Anthropology,School of Life Sciences,Fudan University,Shanghai 200438,China [2]Collaborative Innovation Centre for Genetics and Development,School of Life Sciences,Fudan University,Shanghai 200438,China [3]Capital Institute of Pediatrics,Beijing 100020,China [4]Center for Genetic and Genomic Analysis,Genesky Biotechnologies Inc.,Shanghai 201203,China [5]Institute of Reproduction and Development in Obstetrics and Gynaecology Hospital,Fudan University,Shanghai 200011,China

出　　处：《Reproductive and Developmental Medicine》2017年第3期127-133,共7页生殖与发育医学（英文版）

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].

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.

关 键 词：GLI Family Zinc Finger 2 Neural Tube Defects rs3738880 Sonic Hedgehog Pathway 

分 类 号：F42[经济管理—产业经济]