Na So Young, Park Sung Sup, Seo Jeong Kee
Department of Pediatrics, College of Medicine, Seoul National University; Dongguk University, Korea.
J Pediatr Gastroenterol Nutr. 2015 Sep;61(3):285-91. doi: 10.1097/MPG.0000000000000796.
The aim of the present study was to investigate the genetic polymorphisms of the autophagy-associated genes autophagy-related 16-like 1 (ATG16L1), immunity-related GTPase M (IRGM), Unc-51-like kinase 1 (ULK1), and NOD2 with respect to early-onset Crohn disease (CD) among Korean children.
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: ATG16L1 rs2241880, IRGM SNPs [rs13361189, rs4958847, rs1000113, rs10065172, and rs72553867], ULK1 SNPs [rs12303764, rs10902469, and rs7488085], NOD2 SNPs [Arg702Trp and Gly908Arg]; direct sequencing: NOD2 leu1007fsinsC). The onset age of patients was 8.6 ± 4.7 years. Twelve patients (18.5%) had an onset age of <1 year.
Two of the 12 SNPs showed significant results. IRGM 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, P = 0.03) and genotype distribution (dominant model: OR 2.17, 95% CI 1.07-4.39, P = 0.03). IRGM rs72553867 exhibited association with CD with respect to its minor allele frequency (OR 0.50, 95% CI 0.27-0.91, P = 0.02) and genotype distribution (dominant model: OR 0.50, 95% CI 0.23-0.94, P = 0.03). The 3 SNPs of NOD2 existed only as wild types for both groups. In the genotype-phenotype analysis, the onset age, disease location, and disease behavior exhibited no association.
IRGM rs1000113 and IRGM 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.
本研究旨在调查自噬相关基因自噬相关16样蛋白1（ATG16L1）、免疫相关GTP酶M（IRGM）、Unc-51样激酶1（ULK1）和核苷酸结合寡聚化结构域2（NOD2）在韩国儿童早发性克罗恩病（CD）中的基因多态性。
选取2000年1月至2012年5月间首尔国立大学儿童医院的65例CD患者及72例未患病对照。分析12种不同的单核苷酸多态性（SNP）（TaqMan检测法：ATG16L1 rs2241880、IRGM SNP [rs13361189、rs4958847、rs1000113、rs10065172和rs72553867]、ULK1 SNP [rs12303764、rs10902469和rs7488085]、NOD2 SNP [Arg702Trp和Gly908Arg]；直接测序法：NOD2 leu1007fsinsC）。患者发病年龄为8.6±4.7岁。12例患者（18.5%）发病年龄<1岁。
12个SNP中有2个显示出显著结果。IRGM rs1000113的次要等位基因频率与CD存在关联（优势比[OR] 1.71，95%置信区间[CI] 1.05 - 2.79，P = 0.03），基因型分布也有关联（显性模型：OR 2.17，95% CI 1.07 - 4.39，P = 0.03）。IRGM rs72553867的次要等位基因频率与CD存在关联（OR 0.50，95% CI 0.27 - 0.91，P = 0.02），基因型分布也有关联（显性模型：OR 0.50，95% CI 0.23 - 0.94，P = 0.···3）。两组中NOD2的3个SNP均仅以野生型存在。在基因型 - 表型分析中，发病年龄、疾病部位和疾病行为均无关联。
IRGM rs1000113和IRGM rs72553867分别作为风险位点和防御位点与早发性CD存在关联。这表明自噬途径在早发性CD中起重要作用。
