title: Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients.
abstract: Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric nervous system known to be associated with the RET-protooncogene and other candidates. Recently, a genome-wide association study has added NRG1, a regulator of the development of the enteric ganglia precursors, as a new candidate gene. The aim of this study is to validate the association of the RET-protooncogene and the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide polymorphism (SNP) genotyping and PCR-restriction fragment length polymorphism for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene) and rs2439305 (NRG1) showed the strongest associations with the disease at P-values of 8.17E-09 (odds ratio (OR)=6.43, 95% confidence intervals (CI)=3.33-12.40) and 6.94E-03 (OR=3.28, 95% CI=1.28-8.38), respectively. The RET-protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG genotype) was strongly associated with an increased risk of HSCR with a P-value of 1.99E-04 (OR=20.34, 95% CI; 2.54-162.78) when compared with a single SNP of the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and NRG1 is involved in the risk of HSCR development in the Thai population. Moreover, the study also detected a combined effect of SNPs by SNP-SNP interaction, which may help in predicting HSCR risk.
authors.affiliation: Center for Genomics and Bioinformatics Research, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Theerawut
authors.initials: T
authors.lastname: Phusantisampan
authors.forename: Surasak
authors.initials: S
authors.lastname: Sangkhathat
authors.forename: Amornrat
authors.initials: A
authors.lastname: Phongdara
authors.forename: Piyawan
authors.initials: P
authors.lastname: Chiengkriwate
authors.forename: Sakda
authors.initials: S
authors.lastname: Patrapinyokul
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006627:Hirschsprung Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013785:Thailand / Q000208:ethnology; D055815:Young Adult
chemical_list: D020890:Neuregulin-1; D051096:Proto-Oncogene Proteins c-ret