{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:50:11Z","timestamp":1791975011449,"version":"4.4.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012254, 2018A030313570"],"award-info":[{"award-number":["2022A1515012254, 2018A030313570"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Science and Technology Project of Guangzhou","doi-asserted-by":"publisher","award":["201903010074, 202206080002"],"award-info":[{"award-number":["201903010074, 202206080002"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (<jats:italic>ECE1<\/jats:italic>) has been reported to be associated with HSCR. However, the relationship between <jats:italic>ECE1<\/jats:italic> single nucleotide polymorphism (SNP) rs169884 and HSCR in the southern Chinese population remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 in <jats:italic>ECE1<\/jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might control <jats:italic>ECE1<\/jats: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 (<jats:italic>OR\u2009<\/jats:italic>=\u20091.00, <jats:italic>95% CI<\/jats:italic>: 0.89\u223c1.12, <jats:italic>P<jats:sub>adj\u2009<\/jats:sub><\/jats:italic>=\u20090.77) or TCA (<jats:italic>OR\u2009<\/jats:italic>=\u20091.00, <jats:italic>95% CI<\/jats:italic>: 0.72\u223c1.38, <jats:italic>P<jats:sub>adj\u2009<\/jats:sub><\/jats:italic>=\u20090.94), we found that rs169884 could increase the risk of L-HSCR (<jats:italic>OR<\/jats:italic>\u2009=\u20091.23, <jats:italic>95% CI<\/jats:italic> 1.02\u223c1.45, <jats:italic>P<jats:sub>adj\u2009<\/jats:sub><\/jats:italic>=\u20090.024).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggested that rs169884 might play a regulatory role for <jats:italic>ECE1<\/jats:italic> expression and increase susceptibility of L-HSCR in southern Chinese children.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.1056938","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T20:56:11Z","timestamp":1671742571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese 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