Combined Genetic Effects of RET and NRG1 Susceptibility Variants on Multifactorial Hirschsprung Disease in Indonesia

摘要

BackgroundSpecific genetic variants atRET(rs2435357) andNRG1(rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect ofRETrs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry. MethodsSixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped forRETrs2506030 using the TaqMan assay. ResultsRETrs2506030 was associated with HSCR both by case-control analysis (odds ratio?=?1.68;P?=?0.043) and the transmission disequilibrium test (P?=?0.034). Furthermore, individuals with five or six risk alleles atRETrs2506030, rs2435357 andNRG1rs7835688 showed ～45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles. ConclusionsDisease risk of HSCR is increased by the combination of specificRETandNRG1susceptibility variants.