Moran Christopher J, Klein Christoph, Muise Aleixo M, Snapper Scott B
*Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts; †Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; ‡Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany; §Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada; ‖SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada; ¶Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts; **Division of Gastroenterology and Hepatology, Brigham & Women's Hospital, Boston, Massachusetts; and ††Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Inflamm Bowel Dis. 2015 May;21(5):1166-75. doi: 10.1097/MIB.0000000000000329.
The pathogenesis of pediatric inflammatory bowel disease (IBD) is only partially understood. Strong evidence implicates a strong genetic component including high monozygotic twin concordance and familial disease phenotype concordance rates. Genome-wide association studies have identified associations between >160 genetic loci and the risk for developing IBD. The roles of implicated genes are largely immune-mediated, although other functions include cellular migration, oxidative stress, and carbohydrate metabolism. Additionally, growing literature describes monogenic causes of IBD that frequently present as infantile or very early-onset IBD. The interplay between IBD risk single nucleotide polymorphisms and rare genetic variants has yet to be determined. Studying patients with very early-onset IBD may elicit genetic factors that could be applied to broader populations of IBD. This review describes what is known about the genetic causes of very early-onset IBD and genetic strategies that may unravel more of the genetic causes of IBD.
儿童炎症性肠病（IBD）的发病机制仅得到部分理解。有力证据表明其存在很强的遗传因素，包括高单卵双胞胎一致性和家族性疾病表型一致性比率。全基因组关联研究已确定超过160个基因位点与患IBD的风险之间存在关联。尽管其他功能包括细胞迁移、氧化应激和碳水化合物代谢，但相关基因的作用主要是免疫介导的。此外，越来越多的文献描述了IBD的单基因病因，这些病因常表现为婴儿期或极早发性IBD。IBD风险单核苷酸多态性与罕见基因变异之间的相互作用尚未确定。研究极早发性IBD患者可能会发现可应用于更广泛IBD人群的遗传因素。本综述描述了关于极早发性IBD遗传病因的已知情况以及可能揭示更多IBD遗传病因的遗传策略。
