Ke Juntao, Zeng Shuaidan, Mao Jianxiong, Wang Jianyao, Lou Jiao, Li Jiaoyuan, Chen Xueqin, Liu Cheng, Huang Liu-Ming, Wang Bin, Liu Lei
Department of General Surgery, Shenzhen Children Hospital, Shenzhen, China; State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment & Health, Ministry of Environmental Protection Key Laboratory of Environment and Health (Wuhan), and Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of General Surgery, Shenzhen Children Hospital, Shenzhen, China.
J Pediatr Surg. 2016 Oct;51(10):1661-4. doi: 10.1016/j.jpedsurg.2016.05.009. Epub 2016 May 31.
Biliary atresia (BA) is a major neonatal cholestatic disease and main indication for pediatric liver transplantation in the world. Recently, GPC1 has been implicated as a risk gene for BA by genetic studies and follow-up functional experiments on zebrafish.
Two common genetic variants of GPC1, rs2292832 and rs3828336, were selected systematically through 'SNPinfo', and were examined using TaqMan Genotyping Assays for association studies in a Chinese population containing 134 cases and 618 controls.
Of the two single nucleotide polymorphisms (SNPs), we found a significantly decreased BA risk associated with rs2292832 (additive model: OR=0.638, 95% CI: 0.467-0.873, P=0.005), and a marginal effect for rs3828336 (heterozygous model: OR=0.564, 95% CI: 0.312-1.020, P=0.058). The haplotype analysis indicated that either Crs2292832-Crs3828336&Trs3828336 or Trs2292832-Trs3828336 conferred a protective effect from BA (OR=0.569, 95% CI=0.414-0.783, P<0.001; OR=0.528, 95% CI: 0.301-0.926, P=0.026). Moreover, bioinformatics analysis suggested that rs2292832 altered GPC1 expression via effect on transcription-factor-binding sites (TFBS) of upstream binding transcription factor (UBTF), as a regulatory DNA variation in Deoxyribonuclease I (DNase I) hypersensitive sites (DHSs).
Common variants of GPC1 gene were genetically involved in BA risk.
胆道闭锁（BA）是一种主要的新生儿胆汁淤积性疾病，也是全球儿童肝移植的主要指征。最近，通过基因研究以及对斑马鱼的后续功能实验，GPC1被认为是BA的一个风险基因。
通过“SNPinfo”系统筛选出GPC1的两个常见基因变异体rs2292832和rs3828336，并使用TaqMan基因分型检测法对一个包含134例病例和618例对照的中国人群进行关联研究。
在这两个单核苷酸多态性（SNP）中，我们发现与rs2292832相关的BA风险显著降低（加性模型：OR = 0.638，95%CI：0.467 - 0.873，P = 0.005），而rs3828336有边缘效应（杂合子模型：OR = 0.564，95%CI：0.312 - 1.020，P = 0.058）。单倍型分析表明，Crs2292832 - Crs3828336&Trs3828336或Trs2292832 - Trs3828336均可对BA起到保护作用（OR = 0.569，95%CI = 0.414 - 0.783，P < 0.001；OR = 0.528，95%CI：0.301 - 0.926，P = 0.026）。此外，生物信息学分析表明，rs2292832通过影响上游结合转录因子（UBTF）的转录因子结合位点（TFBS）来改变GPC1的表达，作为脱氧核糖核酸酶I（DNase I）超敏位点（DHS）中的一个调控性DNA变异。
GPC1基因的常见变异与BA风险存在遗传关联。
