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

Background: Specific genetic variants at RET (rs2435357) and NRG1 (rs7835688, rs16879552) are associated with Hirschsprung disease (HSCR) in Indonesia. This study aimed to investigate the additional effect of RET rs2506030 on these variants to determine its potential interactions in HSCR patients of Indonesian ancestry.

Methods: Sixty HSCR patients and 122 non-HSCR controls were ascertained for this study and genotyped for RET rs2506030 using the TaqMan assay.

Results: RET rs2506030 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 at RET rs2506030, rs2435357 and NRG1 rs7835688 showed ∼45-fold higher HSCR risk than those with 0 or 1 or 2 risk alleles.

Conclusions: Disease risk of HSCR is increased by the combination of specific RET and NRG1 susceptibility variants.