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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*,‖,¶

doi: 10.1002/ibd.22972
Original Basic Science Articles

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.

Article first published online 16 April 2012

*Department of Internal Medicine, Graduate School, Yonsei University College of Medicine, Seoul, Republic of Korea

Division of Gastroenterology, Department of Internal Medicine, Myongji Hospital, Kwandong University College of Medicine, Goyang, Republic of Korea

Cardiovascular Genome Center, Yonsei University College of Medicine, Seoul, Republic of Korea

§Yonsei University Research Institute of Science for Aging, Seoul, Republic of Korea

Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea

Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

**Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea

††Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.

Reprints: Jae Hee Cheon, MD, PhD, Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea (e-mail: geniushee@yuhs.ac) or Dong-Jik Shin, PhD, Cardiovascular Genome Center, Yonsei University College of Medicine, Yonsei University Research Institute of Science for Aging, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea (e-mail: shindj@yuhs.ac).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

Supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: 2010-006490).

Received March 5, 2012

Accepted March 14, 2012

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