Li Qi, Zhang Zhen, Diao Mei, Gan Liang, Cheng Wei, Xiao Ping, Su Lin, Shangguan Shaofang, Jiang Qian, Li Long
*Graduate School of Peking Union Medical College Beijing, China †Department of General Surgery, Capital Institute of Pediatrics Beijing, China ‡Department of Surgery, Beijing United Family Hospital, Beijing, China §Department of Paediatrics and Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia ||Department of Pathology, Capital Institute of Pediatrics Affiliated Children's Hospital ¶Reproductive Medicine Center, Clinical College of PLA Affiliated Anhui Medical University, Hefei #Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics **Department of Medical Genetics, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
J Pediatr Gastroenterol Nutr. 2017 Mar;64(3):385-390. doi: 10.1097/MPG.0000000000001263.
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.
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.
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).
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.
先天性巨结肠症（HSCR）是一种先天性的肠肌层和黏膜下神经丛神经节缺失症，可影响不同长度的肠道。HSCR的发病率约为每5000例活产中有1例；然而，由于RET、SEMA3和NRG1基因座的单核苷酸多态性（SNP），其风险存在显著的个体差异。本研究调查了这些变异对中国人群疾病发展和表型的影响。
使用TaqMan基因分型检测法，对由115例HSCR患者和117例未受影响的对照组成的队列中的6个SNP进行基因分型。在DNA提取前对所有样本进行受影响节段长度（短、长或全结肠无神经节症）的组织学鉴定。
RET基因的rs2435357和rs2506030以及SEMA3基因的rs12707682赋予了显著的遗传风险。此外，HSCR患者的平均累积风险评分显著高于对照组。通过按效应大小评估风险等位基因，个体被分为3个加权风险评分组：低（≤3）、中（4）和高（≥5）。高分组个体比低分组个体患HSCR的易感性显著更高，优势比为7.7（95%置信区间3.7 - 16.3）。
累积遗传风险在携带零个和超过5个累积易感等位基因的新生儿之间相差超过35倍。SNP rs2435357、rs2506030和rs12707682可能有助于将中国人群分为不同的风险组。
