Wang Yirui, Sun Yimin, Huang Yongqing, Pan Yongchu, Shi Bing, Ma Jian, Ma Lan, Lan Feifei, Zhou Yuxi, Shi Jiayu, Zhu Jinfang, Jiang Hongbing, Zhang Lei, Xiao Xue, Jiang Min, Yin Aihua, Yu Lili, Wang Lin, Cheng Jing, Yang Yinxue
Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, People's Republic of China.
J Genet. 2017 Sep;96(4):687-693. doi: 10.1007/s12041-017-0808-5.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect due to abnormal orofacial development. Previous studies report abnormal sonic hedgehog (SHH) signalling activity during NSCL/P pathogenesis and propose several genes in the SHH pathway as candidate risk genes. As such, we focussed on GLI3, a downstream modulator of the SHH pathway. In the present study,we genotyped 34 tag SNPs covering GLI3 and performed association analysis with NSCL/P in 504 cases and 455 healthy controls. Our preliminary results identified risk variants of GLI3 that are associated with NSCL/P susceptibility in a Chinese population. In particular, rs3801161 and its haplotypes rs3801161-rs7785287 displayed significant association with NSCL/P and survived Bonferroni correction for multiple comparisons. The robustness of the association between GLI3 and NSCL/P is worth further examination in the future across different populations.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是一种由于口面部发育异常导致的常见出生缺陷。先前的研究报道了NSCL/P发病机制中异常的音猬因子（SHH）信号活性，并提出SHH通路中的几个基因作为候选风险基因。因此，我们聚焦于SHH通路的下游调节因子GLI3。在本研究中，我们对覆盖GLI3的34个标签单核苷酸多态性（tag SNPs）进行了基因分型，并在504例病例和455名健康对照中进行了与NSCL/P的关联分析。我们的初步结果确定了GLI3的风险变异体，它们与中国人群中的NSCL/P易感性相关。特别是，rs3801161及其单倍型rs3801161-rs7785287与NSCL/P表现出显著关联，并在多重比较的Bonferroni校正后仍具有统计学意义。GLI3与NSCL/P之间关联的稳健性值得未来在不同人群中进一步研究。
