Hirschsprung disease (HSCR) is complex genetic disorder of the enteric nervous system (ENS) characterized by an absence of ganglion cells in various parts of the intestine. The disease has a strong genetic association with RET-protooncogene (RET) and various genes involved in neural crest development. SOX10 is a transcriptional regulator whose expression is essential in the development of the ENS. The association between single-nucleotide polymorphisms (SNPs) in SOX10, rs139883 and rs139884, and sporadic HSCR has not been reported. We evaluated the genetic associations between two SNPs in SOX10 and Thai sporadic HSCR, using a case-control design. The study included 120 HSCR and 242 sex-matched controls whose DNA was genotyped using the RFLP (rs139883) and Taqman SNP genotyping (rs139884) methods. The study found minor allele frequencies (MAF) at 0.25 and 0.24 for rs139883 (allele C) and rs139884 (allele A), respectively. Both SNPs complied with the Hardy-Weinberg equilibrium and were further examined through disease association. The association analysis found that the risk-genotype of rs139883 (CC) was associated with HSCR (odds ratio [OR] 2.09; 95% confidence interval [CI] 1.07-4.08; P=0.03). When a subgroup analysis was performed, CC genotype of the rs139883 was significantly associated with HSCR only in females (OR 5.6; 95% CI 1.1-19.5; P=0.01). Moreover, the long segment disease group significantly harbored the risk genotype at a higher frequency (28.6%) compared to the short HSCR (12.0%, P=0.02). In conclusion, the study suggests a genetic association between rs139883 in SOX10 and Thai-female HSCR.
