常见RET、SEMA3和NRG1易感多态性导致的先天性巨结肠症总体遗传风险的人群差异。
Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms.
作者信息
Kapoor Ashish, Jiang Qian, Chatterjee Sumantra, Chakraborty Prakash, Sosa Maria X, Berrios Courtney, Chakravarti Aravinda
机构信息
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Medical Genetics, Capital Institute of Pediatrics, Beijing 100020, China and.
出版信息
Hum Mol Genet. 2015 May 15;24(10):2997-3003. doi: 10.1093/hmg/ddv051. Epub 2015 Feb 9.
The risk of Hirschsprung disease (HSCR) is ∼15/100 000 live births per newborn but has been reported to show significant inter-individual variation from the effects of seven common susceptibility alleles at the RET, SEMA3 and NRG1 loci. We show, by analyses of these variants in 997 samples from 376 HSCR families of European ancestry, that significant genetic risk can only be detected at RET (rs2435357 and rs2506030) and at SEMA3 (rs11766001), but not at NRG1. RET rs2435357 also showed significant frequency differences by gender, segment length of aganglionosis and familiality. Further, in combination, disease risk varied >30-fold between individuals with none and up to 6 susceptibility alleles. Thus, these polymorphisms can be used to stratify the newborn population into distinct phenotypic classes with defined risks to understand HSCR etiology.
先天性巨结肠（HSCR）的发病风险约为每10万例活产新生儿中有15例，但据报道，由于RET、SEMA3和NRG1基因座上7个常见易感等位基因的影响，个体间存在显著差异。通过对来自376个欧洲血统HSCR家族的997个样本中的这些变体进行分析，我们发现，只有在RET（rs2435357和rs2506030）和SEMA3（rs11766001）基因座上才能检测到显著的遗传风险，而在NRG1基因座上则检测不到。RET rs2435357在性别、无神经节段长度和家族性方面也表现出显著的频率差异。此外，综合来看，无易感等位基因和有多达6个易感等位基因的个体之间的疾病风险差异超过30倍。因此，这些多态性可用于将新生儿群体分层为具有明确风险的不同表型类别，以了解HSCR的病因。
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