Cumulative Risk Impact of RET, SEMA3, and NRG1 Polymorphisms Associated With Hirschsprung Disease in Han Chinese
Cumulative Risk Impact of RET, SEMA3, and NRG1 Polymorphisms Associated With Hirschsprung Disease in Han Chinese
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RET、SEMA3 和 NRG1 多态性与汉族先天性巨结肠相关的累积风险影响
DOI：
10.1097/mpg.0000000000001263
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发表时间：
2017-03-01
影响因子：
2.9
通讯作者：
Li, Long
中科院分区：
文献类型：
--
作者：
Li, Qi;Zhang, Zhen;Li, Long
目的：先天性巨结肠症（HSCR）是一种累及不同长度小肠的先天性肌间神经丛和粘膜下神经丛无神经节细胞症。HSCR的发病率约为1/5000活产婴儿;然而，风险显示由RET、SEMA 3和NRG 1基因座的单核苷酸多态性（SNP）引起的显著个体差异。本研究探讨了这些变异对疾病的发展和表型在中国population.Methods的影响：在总数，6个SNPs基因分型在一个队列中，包括115例HSCR患者和117名未受影响的控制使用TaqMan基因分型检测。组织学鉴定的受影响的段长度（短，长，或总结肠无神经节细胞增生症）进行了所有的样品前DNA extraction.Results：重大遗传风险赋予rs 2435357和rs 2506030在RET和rs 12707682在SEMA 3。此外，HSCR患者的平均累积风险评分显著高于对照组。通过效应量对风险等位基因的评估，将个体分为3个加权风险评分组：低（3），中（4）和高（5）。高水平组的个体比低水平组的个体更易患HSCR，比值比为7.7（95%置信区间3.7-16.3）。结论：在具有0和>5个累积易感等位基因的新生儿之间，累积遗传风险变化>35倍。SNPs rs 2435357、rs 2506030和rs 12707682可能有助于将中国人群划分为不同的风险组。
Objectives:Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses affecting a variable length of the intestine. The incidence of HSCR is approximately 1 of 5000 live births; however, the risk shows remarkable individual variation caused by single nucleotide polymorphisms (SNPs) at the RET, SEMA3, and NRG1 loci. The present study investigated the effects of these variants on the disease development and phenotype in a Chinese population.Methods:In total, 6 SNPs were genotyped in a cohort consisting of 115 patients with HSCR and 117 unaffected controls using a TaqMan genotyping assay. Histological identification of the affected-segment length (short, long, or total colonic aganglionosis) was performed for all of the samples before DNA extraction.Results:Significant genetic risk was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3. In addition, the average cumulative risk score in the patients with HSCR was significantly higher than that in the controls. Through the assessment of risk alleles by effect size, individuals were classified into 3 weighted risk score groups: low (3), medium (4), and high (5). Individuals in the high group were significantly more susceptible to HSCR than those in the low group with an odds ratio of 7.7 (95% confidence interval 3.7-16.3).Conclusions:Cumulative genetic risk varied >35-fold between newborns with zero and >5 accumulated susceptibility alleles. The SNPs rs2435357, rs2506030, and rs12707682 may be useful for stratifying the Chinese population into distinct risk groups.