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

14 Pages Posted: 30 Jul 2018

See all articles by Zefeng Lin

Zefeng Lin

Guangzhou Medical University - Department of Pediatric Surgery

Huiting Lin

Guangzhou Medical University - Department of Pediatric Surgery

Jing He

Guangzhou Women and Children's Medical Center

Ming Fu

Guangzhou Medical University - Department of Pediatric Surgery

Liang Su

Guangzhou Medical University - Department of Pediatric Surgery

Yanlu Tong

Guangzhou Medical University - Department of Pediatric Surgery

Hongjiao Chen

Guangzhou Medical University - Department of Pediatric Surgery

Hezhen Wang

Guangzhou Medical University - Department of Pediatric Surgery

Jinglu Zhao

Guangzhou Medical University - Department of Pediatric Surgery

Yan Zhang

Guangzhou Medical University - Department of Pediatric Surgery

Ruizhong Zhang

Guangzhou Medical University - Department of Pediatric Surgery

Huimin Xia

Guangzhou Medical University - Division of Birth Cohort Study; Guangzhou Medical University - Department of Neonatal Surgery

More...

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.

Suggested Citation

Lin, Zefeng and Lin, Huiting and He, Jing and Fu, Ming and Su, Liang and Tong, Yanlu and Chen, Hongjiao and Wang, Hezhen and Zhao, Jinglu and Zhang, Yan and Zhang, Ruizhong and Xia, Huimin, Association of CD14 and NOTCH2 Genetic Polymorphisms with Biliary Atresia in a Southern Chinese Population (July 25, 2018). Available at SSRN: https://ssrn.com/abstract=3220092 or http://dx.doi.org/10.2139/ssrn.3220092

Zefeng Lin

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Huiting Lin

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Jing He

Guangzhou Women and Children's Medical Center ( email )

9 Jinsui Road
Tianhe
Guangzhou, Guangdong 510623
China
+862038076560 (Phone)

Ming Fu

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Liang Su

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Yanlu Tong

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Hongjiao Chen

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Hezhen Wang

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Jinglu Zhao

Guangzhou Medical University - Department of Pediatric Surgery

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Yan Zhang (Contact Author)

Guangzhou Medical University - Department of Pediatric Surgery ( email )

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Ruizhong Zhang

Guangzhou Medical University - Department of Pediatric Surgery ( email )

195 Dongfeng W Rd
Yuexiu Qu
Guangzhou Shi, Guangdong Sheng 510000
China

Huimin Xia

Guangzhou Medical University - Division of Birth Cohort Study ( email )

Guangzhou
China

Guangzhou Medical University - Department of Neonatal Surgery ( email )

Guangzhou
China

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