Juntao Ke1, Shuaidan Zeng2, Jianxiong Mao2, Jianyao Wang2, Jiao Lou3, Jiaoyuan Li3, Xueqin Chen3, Cheng Liu3, Liu-Ming Huang4, Bin Wang5, Lei Liu6. 1. 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. 2. Department of General Surgery, Shenzhen Children Hospital, Shenzhen, China. 3. 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. 4. Department of Pediatric Surgery, BaYi Children's hospital, The military general hospital of Beijing, Beijing, China. Electronic address: surhlm@126.com. 5. Department of General Surgery, Shenzhen Children Hospital, Shenzhen, China. Electronic address: szwb1967@126.com. 6. Department of General Surgery, Shenzhen Children Hospital, Shenzhen, China. Electronic address: liulei3322@aliyun.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Common variants of GPC1 gene were genetically involved in BA risk.
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSION: Common variants of GPC1 gene were genetically involved in BA risk.
Authors: Lin He; Patrick Ho Yu Chung; Vincent Chi Hang Lui; Clara Sze Man Tang; Paul Kwong Hang Tam Journal: Int J Mol Sci Date: 2022-04-27 Impact factor: 6.208