Department of Internal Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea.
Inflamm Bowel Dis. 2013 Jan;19(1):106-14. doi: 10.1002/ibd.22972.
Recent European ancestry genome-wide association studies have identified genetic variants of IRGM as significant susceptibility loci for Crohn's disease (CD). Therefore, we investigated whether genetic variants of IRGM confer genetic susceptibility to CD or ulcerative colitis (UC) and evaluated the genotype-phenotype associations in the Korean population.
This study included 510 inflammatory bowel disease (IBD) patients (253 patients with CD and 257 with UC) and 520 healthy controls in Koreans. Initially, we performed direct sequencing analysis to identify unique IRGM single nucleotide polymorphisms (SNPs). Three selected haplotype-tagging SNPs and one risk locus (rs72553867, rs10065172, rs4958847, and rs12654043) within the IRGM were then geno-typed in patients and controls.
IRGM SNP rs10065172 was significantly associated with CD susceptibility in terms of allelic frequency (P = 0.004; odds ratio [OR] = 1.42) and genotype frequency (dominant model, P = 0.008; OR = 1.62). We also found a relationship between SNP rs72553867 and CD susceptibility in the analysis of allelic frequency (P = 0.0117; OR = 0.67) and genotype frequency (dominant model, P = 0.002; OR = 0.55). In addition, we observed that the association of CD with rs10065172 became stronger in patients with younger age at diagnosis (≤ 20 years) or male gender. However, there was no significant association between the four SNPs and UC susceptibility.
This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population.
最近的欧洲裔全基因组关联研究发现，IRGM 的遗传变异是克罗恩病（CD）的重要易感基因位点。因此，我们研究了 IRGM 的遗传变异是否会导致 CD 或溃疡性结肠炎（UC）的遗传易感性，并评估了韩国人群中的基因型-表型相关性。
本研究纳入了 510 名炎症性肠病（IBD）患者（253 名 CD 患者和 257 名 UC 患者）和 520 名韩国健康对照者。我们首先进行直接测序分析，以鉴定独特的 IRGM 单核苷酸多态性（SNP）。然后，在患者和对照者中对三个选定的单体型标签 SNP 和一个 IRGM 内的风险位点（rs72553867、rs10065172、rs4958847 和 rs12654043）进行基因分型。
IRGM SNP rs10065172 的等位基因频率（P = 0.004；优势比[OR] = 1.42）和基因型频率（显性模型，P = 0.008；OR = 1.62）与 CD 易感性显著相关。我们还发现 SNP rs72553867 与 CD 易感性之间存在关联，表现在等位基因频率分析中（P = 0.0117；OR = 0.67）和基因型频率（显性模型，P = 0.002；OR = 0.55）。此外，我们观察到，在诊断年龄≤20 岁或男性的 CD 患者中，rs10065172 与 CD 的相关性更强。然而，这四个 SNP 与 UC 易感性之间没有显著关联。
这是首次在亚洲人群中发现 IRGM 的 SNP rs10065172 和 rs72553867 是 CD 的主要易感基因位点。
