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Original Research: ASTHMA |

Association of IL-17RB Gene Polymorphism With Asthma

Ji-Sun Jung, BS; Byung Lae Park, PhD; Hyun Sub Cheong, MS; Joon Seol Bae, PhD; Ji-Hye Kim, MS; Hun Soo Chang, PhD; TaiYoun Rhim, PhD; Jong-Sook Park, MD; An-Soo Jang, MD; Young-Mok Lee, MD; Ki-Up Kim, MD; Soo-Taek Uh, MD; Ju Ock Na, MD; Yong-Hoon Kim, MD; Choon-Sik Park, MD, PhD; Hyoung Doo Shin, PhD
Author and Funding Information

*From the Genome Research Center for Allergy and Respiratory Disease (Drs. Chang, J.-S. Park, Jang, and C.-S. Park, and Ms. Jung and Ms. J. -H. kim), Soonchunhyang University Bucheon Hospital, Bucheon, Korea; the Division of Allergy and Respiratory Medicine (Drs. Lee, K.-U. Kim, and Uh), Soonchunhyang University Seoul Hospital, Seoul, Korea; the Division of Allergy and Respiratory Medicine (Drs. Na and Y.-H. Kim), Soonchunhyang University Chunan Hospital, Chunan, Korea; Hanyang University (Dr. Rhim), Seoul, Korea; the Department of Genetic Epidemiology (Drs. B.L. Park and Bae, and Mr. Cheong), SNP Genetics, Inc, Seoul, Korea; and the Department of Life Science (Dr. Shin), Sogang University, Seoul, Korea.

Correspondence to: Choon-Sik Park, MD, PhD, Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon-Si, Kyeonggi-Do, Korea 420-020; e-mail: mdcspark@unitel.co.kr

†Ms. Jung and Dr. B.L. Park contributed equally to this work as the first coauthors.


This study was supported by the grants of the Korea Health 21 R&D Project (Ministry of Health, Welfare and Family Affairs, Republic of Korea, A010249). B-cell lines were provided from the biobank of Soonchunhyang University Bucheon Hospital.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(5):1173-1180. doi:10.1378/chest.08-1595
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Background:  Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL-17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-κB.

Objectives:  We examined the association of polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the effects of those polymorphisms on the transcription of various IL-17RB isoforms.

Methods:  In total, 954 asthmatic patients or 265 healthy control subjects were screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA expression IL-17RB in B-cell lines derived from patients was also measured by reverse transcription-polymerase chain reaction.

Results:  Direct sequencing of 24 unrelated Korean DNA samples revealed 18 genetic variants, including four insertion/deletions and 14 single-nucleotide polymorphisms (SNPs). Six of the SNPs (−1465G>A, +5661G>A, +6297T>C [Y123Y], +13797C>T, +18661C>T, and +18965G>A) were used to screen a larger group of subjects. Intronic polymorphism +5661G>A was significantly associated with the development of asthma (p = 0.001); moreover, a minor allele of IL-17RB +5661G>A appeared at a lower frequency in the asthmatic patients than in the healthy control subjects (0.13 vs 0.19, respectively). The IL-17RB messenger RNA expression in B cells homozygous for IL-17RB+ 5661GG was significantly higher than that in B cells homozygous for IL-17RB+5661AA (p = 0.002).

Conclusions:  A rare allele of IL-17RB +5661G>A may have a protective role against the development of asthma via regulation at the level of transcription. The SNPs identified in this study may be used to develop markers to assess the risk of asthma.

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