Yang Min, Xiong Min, Chen Huan, Geng Lanlan, Chen Peiyu, Xie Jing, Ye Shui Qing, Li Ding-You, Gong Sitang
Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, China.
Division of Experimental and Translational Genetics, Children's Mercy Hospital, University of Missouri Kansas City School of Medicine, 2401 Gillham Road, Kansas City, MO 64108, USA.
Nutrients. 2017 Apr 15;9(4):390. doi: 10.3390/nu9040390.
Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets.
To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy.
A total of 91,024 variants were identified. By filtering out 'normal variants' against those of the 1000 Genomes Project, we identified 12,741 remaining variants which are potentially associated with RES plus food allergy. Among these variants, there are 11,539 single nucleotide polymorphisms (SNPs), 627 deletions, 551 insertions and 24 mixture variants. These variants are located in 1370 genes. They are enriched in biological processes or pathways such as cell adhesion, digestion, receptor metabolic process, bile acid transport and the neurological system. By the PubMatrix analysis, 50 out of the top 100 genes, which contain most variants, have not been previously associated with any of the 17 allergy-associated diseases. These 50 genes represent newly identified allergy-associated genes. Those variants of 627 deletions and 551 insertions have also not been reported before in RES with food allergy.
Exome-seq is potentially a powerful tool to identify potential new biomarkers for RES with food allergy. This study has identified a number of novel genetic variants, opening new avenues of research in RES plus food allergy. Additional validation in larger and different patient populations and further exploration of the underlying molecular mechanisms are warranted.
难治性食管狭窄（RES）可能归因于食物过敏。其病因和发病机制尚未完全明确。通过外显子组测序（外显子组测序）鉴定与该疾病相关的新基因变异可能会提供新的机制见解和新的治疗靶点。
为了鉴定新的和与疾病相关的变异，在Illumina NGS平台上对三名患有RES以及食物过敏的儿童进行了全外显子组测序。
共鉴定出91,024个变异。通过与千人基因组计划的变异进行比对，筛选出“正常变异”后，我们确定了12,741个剩余变异，这些变异可能与RES加食物过敏相关。在这些变异中，有11,539个单核苷酸多态性（SNP）、627个缺失、551个插入和24个混合变异。这些变异位于1370个基因中。它们在细胞黏附、消化、受体代谢过程、胆汁酸转运和神经系统等生物过程或途径中富集。通过PubMatrix分析，在前100个包含大多数变异的基因中，有50个以前未与17种过敏相关疾病中的任何一种相关联。这50个基因代表新鉴定的过敏相关基因。那些627个缺失和551个插入的变异在伴有食物过敏的RES中也未曾报道过。
外显子组测序可能是一种强大的工具，用于识别伴有食物过敏的RES的潜在新生物标志物。本研究鉴定了许多新的基因变异，为RES加食物过敏的研究开辟了新途径。需要在更大且不同的患者群体中进行额外验证，并进一步探索潜在的分子机制。
