title: Effects of RET, NRG1 and NRG3 Polymorphisms in a Chinese Population with Hirschsprung Disease.
abstract: The RET proto-oncogene was identified as a major locus involved in Hirschsprung disease (HSCR). A genome-wide association study (GWAS) and whole exome sequencing identified NRG1 and NRG3 as additional HSCR susceptibility loci. We investigated the effects of RET (rs2506030 and rs2435357), NRG1 (rs2439302, rs16879552 and rs7835688) and NRG3 (rs10748842, rs10883866 and rs6584400) polymorphisms in a Chinese population with HSCR. We assessed single nucleotide polymorphisms (SNPs) in the RET, NRG1 and NRG3 genes in a cohort of 362 sporadic HSCR patients and 1,448 normal controls using a TaqMan genotyping assay. Significant associations were found between HSCR risk and rs2506030, rs2435357, rs2439302 and rs7835688 (odds ratio [OR] 1.64, P = 1.72E-06; 2.97, P = 5.15E-33; 1.84, P = 9.36E-11; and 1.93, P = 1.88E-12, respectively). Two locus analyses of SNPs indicated increased disease risks of HSCR between NRG1 rs2439302 and RET rs2435357 or rs2506030. RET rs2506030 (GG genotype) and rs2435357 (TT genotype), in combination with NRG1 rs2439302 (GG genotype), were strongly associated with the highest risk of HSCR (OR = 56.53, P = 4.50E-07) compared with the two loci or a single SNP of either RET or NRG1. Our results support the association between genetic variation of RET and NRG1 and susceptibility to HSCR in the Chinese population.
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pediatric Surgery, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430015, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Cao
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shao-Tao
authors.initials: ST
authors.lastname: Tang
mesh_terms: D000483:Alleles; D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D020880:Neuregulins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; C094131:NRG1 protein, human; C486357:NRG3 protein, human; D020890:Neuregulin-1; D020880:Neuregulins; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human