Association of CD14 and NOTCH2 Genetic Polymorphisms with Biliary Atresia in a Southern Chinese Population

Abstract

Background: Biliary atresia (BA) is the most common cause of end-stage liver disease in infants with poor prognosis and high mortality. The etiology of BA is still unknown, but the genetic factors have been considered as an important player in BA. Methods: We investigated the association of CD14 (rs2569190) and NOTCH2 (rs835576) with BA susceptibility using the largest case-control cohort, totaling with 506 BA patients and 1473 healthy controls in a Southern Chinese population. The variants were genotyped using the MassARRAY iPLEX Gold system. The association of CD14 (rs2569190) and NOTCH2 (rs835576) with BA risk was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The abnormal expression of CD14 and NOTCH2 in BA patients was analyzed with quantitative RT-PCR and further verified by Western blot. Results: Significant epistatic interaction between the two variants in our samples was observed (P= 8.1E-03, OR= 2.78, 95% CI: 1.32~5.88). The quantitative RT-PCR results showed that the expression of CD14 and NOTCH2 in BA group was significantly lower than that in CC group (0.31±0.02 vs. 1.00±0.14, P<0.001). Conclusions: Though the associations of CD14 (rs2569190) and NOTCH2 (rs835576) SNPs failed to replicate, the interaction between these two expression regulatory SNPs was further identified. The expression of CD14 and NOTCH2 is significantly decreased in BA patients, which might be related to the genetic susceptibility of the genes awaiting for further validation. Funding Information: This study was supported by the grant of National Natural Science Foundation of China (Grant No. 81770510, 81771629, and 81671498) and the Science and Technology Project of Guangzhou (Grant No. 201707010014). Competing Interest Declaration: The authors declare no competing financial interests. Ethical Approval Statement: This study was approved by the Institutional Review Board of Guangzhou Women and Children’s Medical Center and the experimental process is strictly abided by medical ethics. All participants have signed informed consent.