Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese children

Chaoting Lan; Yanqing Liu; Xiao Wu; Bingtong Wang; Songqing Xin; Qiuming He; Wei Zhong; Zipeng Liu

doi:10.3389/fped.2022.1056938

Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese children

Front Pediatr. 2022 Dec 22:10:1056938. doi: 10.3389/fped.2022.1056938. eCollection 2022.

Authors

Chaoting Lan¹, Yanqing Liu¹, Xiao Wu², Bingtong Wang², Songqing Xin³, Qiuming He¹, Wei Zhong¹, Zipeng Liu¹

Affiliations

¹ Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
² Guangzhou Women and Children's Medical Center, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Medical University, Guangzhou, China.
³ Changan Hospital of Dongguan, Dongguan, China.

Abstract

Background: Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (ECE1) has been reported to be associated with HSCR. However, the relationship between ECE1 single nucleotide polymorphism (SNP) rs169884 and HSCR in the southern Chinese population remains unknown.

Methods: 1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 in ECE1 was genotyped in all samples. We tested the association between rs169884 and HSCR under various genetic models. We also evaluated the effect of rs169884 on HSCR subtypes, including short-segment HSCR (S-HSCR), long-segment HSCR (L-HSCR) and total colonic aganglionosis (TCA). External epigenetic data were integrated to investigate the potential biological function of rs169884.

Results: Chromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might control ECE1 expression through regulating its enhancer function. We did not find a significant association between rs169884 and HSCR. For HSCR subtypes, although no significant associations were detected between rs169884 and S-HSCR (OR = 1.00, 95% CI: 0.89∼1.12, P_adj = 0.77) or TCA (OR = 1.00, 95% CI: 0.72∼1.38, P_adj = 0.94), we found that rs169884 could increase the risk of L-HSCR (OR = 1.23, 95% CI 1.02∼1.45, P_adj = 0.024).

Conclusion: These results suggested that rs169884 might play a regulatory role for ECE1 expression and increase susceptibility of L-HSCR in southern Chinese children.

Keywords: Endothelin Converting Enzyme-1; HSCR subtypes; Hirschsprung's disease; epigenetic regulation; single nucleotide polymorphism.