Association of IL-17RB Gene Polymorphism With Asthma

作者：Jung Ji Sun; Park Byung Lae; Cheong Hyun Sub; Bae Joon Seol; Kim Ji Hye; Chang Hun Soo; Rhim TaiYoun; Park Jong Sook; Jang An Soo; Lee Young Mok; Kim Ki Up; Uh Soo Taek; Na Ju Ock; Kim Yong Hoon; Park Choon Sik^*; Shin Hyoung Doo

来源：Chest, 2009, 135(5): 1173-1180.

DOI：10.1378/chest.08-1595

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-kappa B.
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 II-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 IS 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. (CHEST 2009; 135:1173-1180)

• 出版日期2009-5