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Hirschsprung disease (HSCR) is the most frequent genetic cause of congenital intestinal obstruction with an incidence of 1:5000 live births. In a pathway-based epistasis analysis of data generated by genome-wide association study on HSCR, specific genotype of Patched 1 (PTCH1) has been linked to an increased risk for HSCR. The aim of the present study is to examine the contribution of genetic variants in PTCH1 to the susceptibility to HSCR in Han Chinese. Accordingly, we assessed 8 single nucleotide polymorphisms (SNPs) within PTCH1 gene in 104 subjects with sporadic HSCR and 151 normal controls of Han Chinese origin by the Sequenom MassArray technology (iPLEX GOLD). Two of the eight genetic markers were found to be significantly associated with Hirschsprung disease (rs357565, allele P = 0.005; rs2236405, allele P = 0.002, genotype P = 0.003). Both the C allele of rs357565 and the A allele of rs2236405 served as risk factors for HSCR. During haplotype analysis, one seven-SNP-based haplotype was the most significant, giving a global P = 0.0036. Our results firstly suggest common variations of PTCH1 may be involved in the altered risk for HSCR in the Han Chinese population, providing potential molecular markers for early diagnosis of Hirschsprung disease. [ABSTRACT FROM AUTHOR]