Common genetic variants of GPC1 gene reduce risk of biliary atresia in a Chinese population

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 C rs2292832 -C rs3828336 &T rs3828336 or T rs2292832 -T rs3828336 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.