Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China ; Shanghai Institute for Pediatric Research, Shanghai, China.
PLoS One. 2013 Sep 20;8(9):e75407. doi: 10.1371/journal.pone.0075407. eCollection 2013.
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.
先天性巨结肠症（HSCR）是最常见的遗传原因导致的先天性肠梗阻，发病率为每 5000 例活产儿中有 1 例。在对 HSCR 的全基因组关联研究数据进行基于途径的上位性分析中，发现 Patched 1（PTCH1）的特定基因型与 HSCR 的风险增加有关。本研究旨在探讨 PTCH1 中的遗传变异对汉族人群发生 HSCR 的易感性的影响。因此，我们通过Sequenom MassArray 技术（iPLEX GOLD）评估了 104 例散发性 HSCR 患者和 151 例汉族正常对照者 PTCH1 基因内的 8 个单核苷酸多态性（SNP）。发现其中两个遗传标记与先天性巨结肠症显著相关（rs357565，等位基因 P = 0.005；rs2236405，等位基因 P = 0.002，基因型 P = 0.003）。rs357565 的 C 等位基因和 rs2236405 的 A 等位基因均为 HSCR 的危险因素。在单体型分析中，一个基于 7 个 SNP 的单体型最显著，全局 P = 0.0036。我们的研究结果首次表明，PTCH1 的常见变异可能与汉族人群 HSCR 风险的改变有关，为先天性巨结肠症的早期诊断提供了潜在的分子标志物。
