Genetic Polymorphisms in Autophagy-Associated Genes in Korean Children With Early-Onset Crohn Disease. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Na, So Young; Park, Sung Sup; Seo, Jeong Kee
• Is Part Of: Journal of pediatric gastroenterology and nutrition. Volume 61:Issue 3(2015)
• Publication Date: 2015-09
• Subjects: Children -- Nutrition -- Periodicals; Pediatric gastroenterology -- Periodicals; Infants -- Nutrition -- Periodicals; Nutrition disorders in children -- Periodicals; Child Nutrition -- Periodicals; Digestive System -- growth & development -- Periodicals; Gastrointestinal Diseases -- Periodicals; Infant Nutrition -- Periodicals; Nutrition Disorders -- Periodicals; Child; 618.923
• DOI: 10.1097/MPG.0000000000000796
• Languages: English
• ISSNs: 0277-2116

Abstract

<abstract> <title>ABSTRACT</title> <sec> <title>Objective:</title> <p>The aim of the present study was to investigate the genetic polymorphisms of the autophagy-associated genes autophagy-related 16-like 1 (<italic>ATG16L1</italic>), immunity-related GTPase M (<italic>IRGM</italic>), Unc-51-like kinase 1 (<italic>ULK1</italic>), and <italic>NOD2</italic> with respect to early-onset Crohn disease (CD) among Korean children.</p> </sec> <sec> <title>Methods:</title> <p>A total of 65 patients with CD from the Seoul National University Children's Hospital, from January 2000 to May 2012, and 72 unaffected controls were selected. Twelve different single nucleotide polymorphisms (SNPs) were analyzed (TaqMan assay: <italic>ATG16L1</italic> rs2241880, <italic>IRGM</italic> SNPs [rs13361189, rs4958847, rs1000113, rs10065172, and rs72553867], <italic>ULK1</italic> SNPs [rs12303764, rs10902469, and rs7488085], <italic>NOD2</italic> SNPs [Arg702Trp and Gly908Arg]; direct sequencing: <italic>NOD2</italic> leu1007fsinsC). The onset age of patients was 8.6 ± 4.7 years. Twelve patients (18.5%) had an onset age of <1 year.</p> </sec> <sec> <title>Results:</title> <p>Two of the 12 SNPs showed significant results. <italic>IRGM</italic> rs1000113 exhibited an association with CD with respect to its minor allele frequency (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.05–2.79, <italic>P</italic> = 0.03) and genotype distribution (dominant model: OR 2.17, 95% CI 1.07–4.39, <italic>P</italic> = 0.03). <italic>IRGM</italic> rs72553867 exhibited association with CD with respect to its minor allele frequency (OR 0.50, 95% CI 0.27–0.91, <italic>P</italic> = 0.02) and genotype distribution (dominant model: OR 0.50, 95% CI 0.23–0.94, <italic>P</italic> = 0.03). The 3 SNPs of <italic>NOD2</italic> existed only as wild types for both groups. In the genotype-phenotype analysis, the onset age, disease location, and disease behavior exhibited no association.</p> </sec> <sec> <title>Conclusions:</title> <p> <italic>IRGM</italic> rs1000113 and <italic>IRGM</italic> rs72553867 exhibited associations with early-onset CD as risk loci and defense loci, respectively. This suggests that the autophagy pathway plays an important role in early-onset CD.</p> </sec> </abstract>