Pharmacogenomics and Personalized Medicine (Aug 2020)
miR-100 rs1834306 A>G Increases the Risk of Hirschsprung Disease in Southern Chinese Children
Abstract
Yun Zhu,* Ao Lin,* Yi Zheng, Xiaoli Xie, Qiuming He, Wei Zhong Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei ZhongDepartment of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, People’s Republic of ChinaTel/ Fax +86-18902268667Email [email protected]: Hirschsprung disease (HSCR) is a rare congenital gastrointestinal disease characterized by the absence of intestinal submucosal and myometrial ganglion cells. Recently, researches indicated that miR-100 regulated the growth, differentiation and apoptosis of neurons, and affected the functions of HSCR-associated pathways. While miR-100 rs1834306 A>G polymorphism was shown to modify the susceptibility to tumors, the association between this polymorphism and HSCR susceptibility is still unknown.Methods: This was a case–control study consisting of 1470 HSCR cases and 1473 controls from southern China. DNA was genotyped by TaqMan real-time PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were used as statistical indicators.Results: We found that miR-100 rs1834306 G allele and GG genotype significantly increased HSCR susceptibility (GG vs AA: adjusted OR=1.31, 95% CI=1.04– 1.64, P=0.020; G vs A: adjusted OR=1.12, 95% CI=1.01– 1.25, P=0.041; GG vs AA/AG: adjusted OR=1.30, 95% CI=1.07– 1.59, P=0.010). In the stratified analysis, miR-100 rs1834306 GG genotype carriers had higher risk to develop HSCR in all clinical subtypes when compared with those with AA/AG genotypes, and OR was rising with HSCR aggravation (SHSCR: adjusted OR=1.28, 95% CI=1.03– 1.59, P=0.029; LHSCR: adjusted OR=1.48, 95% CI=1.06– 2.07, P=0.020; TCA: adjusted OR=2.12, 95% CI=1.22– 3.69, P=0.008).Conclusion: Our findings suggested that miR-100 rs1834306 A>G polymorphism was associated with increased HSCR susceptibility in southern Chinese children. Furthermore, miR-100 rs1834306 GG genotype had a greater genetic pathopoiesis in severe HSCR.Keywords: Hirschsprung disease, miR-100, polymorphism, susceptibility
