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Inflammatory Bowel Diseases:
doi: 10.1002/ibd.22972
Original Basic Science Articles

Associations Between Genetic Variants in the IRGM Gene and Inflammatory Bowel Diseases in the Korean Population

Moon, Chang Mo MD*,†; Shin, Dong-Jik PhD‡,§; Kim, Seung Won MS‖,¶; Son, Nak-Hoon MS‡,**; Park, Ahram BS; Park, Boram BS‡,**; Jung, Eun Suk MD‖,¶; Kim, Eun Soo MD, PhD††; Hong, Sung Pil MD, PhD; Kim, Tae Il MD, PhD*,‖; Kim, Won Ho MD, PhD*,‖,¶; Cheon, Jae Hee MD, PhD*,‖,¶

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population.

© Crohn's & Colitis Foundation of America, Inc.

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