Open AccessAssociation between ABHD1 and DOK6 polymorphisms and susceptibility to Hirschsprung disease in Southern Chinese children
Author(s) -
Lan Chaoting,
Wu Yuxin,
Wang Ning,
Luo Yun,
Zhao Jinglu,
Zheng Yi,
Zhang Yan,
Huang Lihua,
Zhu Yun,
Lu Lifeng,
Zhong Wei,
Zeng Jixiao,
Xia Huimin
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16905
Subject(s) - hirschsprung's disease , genetics , disease , biology , association (psychology) , medicine , psychology , psychotherapist
Hirschsprung disease (HSCR) is an infrequent congenital intestinal dysplasia. The known genetic variations are unable to fully explain the pathogenesis of HSCR. The α/β‐hydratase domain 1 (ABHD1) interferes with the proliferation and migration of intestinal stem cells. Docking protein 6 ( DOK6 ) is involved in neurodevelopment through RET signalling pathway. We examined the association of ABHD1 and DOK6 genetic variants with HSCR using 1470 controls and 1473 HSCR patients from Southern Chinese children. The results clarified that DOK6 rs12968648 G allele significantly increased HSCR susceptibility, in the allelic model ( p = 0.034; OR = 1.12, 95%CI = 1.01~1.24) and the dominant model ( p = 0.038; OR = 1.12, 95%CI = 1.01~1.25). Clinical stratification analysis showed that rs12968648 G allele was associated with increased risk of short‐segment HSCR (S‐HSCR), in the allelic model ( p = 0.028; OR = 1.14, 95%CI = 1.01~1.28) and the additive model ( p = 0.030; OR = 1.14, 95%CI = 1.01~1.28). ABHD1 rs2304678 C allele had higher risk to develop total colonic aganglionosis (TCA) in the allelic model ( p = 7.04E‐03; OR = 1.67, 95%CI = 1.15~2.43) and the dominant model ( p = 4.12E‐03; OR = 1.93, 95%CI = 1.23~3.04). DOK6 rs12968648 and ABHD1 rs2304678 had significant intergenic synergistic effect according to logical regression ( p = 0.0081; OR = 0.76, 95%CI = 0.63~0.93) and multifactor dimensionality reduction (MDR, p = 0.0045; OR = 1.25, 95%CI = 1.07~1.46). This study verified two susceptible variations of HSCR on ABHD1 and DOK6 . Their roles in HSCR should be conducted in further studies.