Potential Association of INMT Nonsynonymous Variant (His46Pro) with Hirschsprung's Disease
Potential Association of INMT Nonsynonymous Variant (His46Pro) with Hirschsprung's Disease
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DOI：
10.1159/000435874
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发表时间：
2015-01-01
期刊：
影响因子：
2.5
通讯作者：
Shin, Hyoung Doo
中科院分区：
文献类型：
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作者：
Kim, Jason Yongha;Seo, Jeong-Meen;Shin, Hyoung Doo
背景：先天性巨结肠症（HSCR）是一种先天性疾病，其特征是部分或整个结肠缺乏神经节细胞，导致肠梗阻等相关症状。最近，我们的小组在韩国 HSCR 病例和对照中进行了一项全基因组关联研究，以鉴定其他基因中的新标记。目的：本研究旨在通过重复研究进一步研究 INMT 与 HSCR 的潜在关联。方法：在 187 名 HSCR 患者和 283 名对照者中，分析了总共 15 个 INMT 单核苷酸多态性 (SNP) 与 HSCR 的关联。还对 HSCR 的亚型（短节段、长节段和全结肠无神经节细胞症）进行了分析。结果：非同义 SNP rs77743549 (His46Pro) 与 HSCR 风险增加显着相关（比值比 = 1.77；校正 p = 0.002）。此外，该 rs77743549 保留了与 HSCR 所有亚型的关联（在共显性模型下，p = 0.006-0.002）。一项全球测试表明 rs77743549 与神经节缺失的长度相关 (p = 0.00004)。结论：虽然需要进一步的复制和功能评估，但我们的研究表明 INMT rs77743549 可能与 HSCR 风险和/或肠神经系统发育相关。 (C) 2015 S. Karger AG，巴塞尔
Background: Hirschsprung's disease (HSCR) is a congenital disorder which is characterized by the lack of ganglion cells in part of or the entire colon, resulting in intestinal obstruction and other related symptoms. Recently, our group has conducted a genome-wide association study in Korean HSCR cases and controls to identify novel markers in other genes. Objectives: The present research aimed to further study the potential association of INMT with HSCR by conducting a replication study. Methods: A total of 15 INMT single nucleotide polymorphisms (SNPs) were analyzed for the association with HSCR in 187 HSCR patients and 283 controls. Analyses were also conducted for subtypes of HSCR (short-segment, long-segment, and total colonic aganglionosis). Results: A nonsynonymous SNP rs77743549 (His46Pro) was significantly associated with the increased risk of HSCR (odds ratio = 1.77; corrected p = 0.002). Furthermore, this rs77743549 retained its association with all subtypes of HSCR (p = 0.006-0.002 under the codominant model). A global test showed that rs77743549 was associated with the length of aganglionosis (p = 0.00004). Conclusion: Although further replications and functional evaluations are needed, our study suggests that rs77743549 of INMT may be associated with the risk for HSCR and/or the development of the enteric nervous system. (C) 2015 S. Karger AG, Basel