AUTHOR=Lan Chaoting , Liu Yanqing , Wu Xiao , Wang Bingtong , Xin Songqing , He Qiuming , Zhong Wei , Liu Zipeng 

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

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.1056938

DOI=10.3389/fped.2022.1056938

ISSN=2296-2360

ABSTRACT=<sec><title>Background</title><p>Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (<italic>ECE1</italic>) has been reported to be associated with HSCR. However, the relationship between <italic>ECE1</italic> single nucleotide polymorphism (SNP) rs169884 and HSCR in the southern Chinese population remains unknown.</p></sec><sec><title>Methods</title><p>1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 in <italic>ECE1</italic> 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.</p></sec><sec><title>Results</title><p>Chromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might control <italic>ECE1</italic> 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 (<italic>OR </italic>= 1.00, <italic>95% CI</italic>: 0.89∼1.12, <italic>P<sub>adj </sub></italic>= 0.77) or TCA (<italic>OR </italic>= 1.00, <italic>95% CI</italic>: 0.72∼1.38, <italic>P<sub>adj </sub></italic>= 0.94), we found that rs169884 could increase the risk of L-HSCR (<italic>OR</italic> = 1.23, <italic>95% CI</italic> 1.02∼1.45, <italic>P<sub>adj </sub></italic>= 0.024).</p></sec><sec><title>Conclusion</title><p>These results suggested that rs169884 might play a regulatory role for <italic>ECE1</italic> expression and increase susceptibility of L-HSCR in southern Chinese children.</p></sec>