Association of IL-17RB gene polymorphism with asthma.
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-kappaB.


OBJECTIVE
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.
Jung
Ji-Sun
JS
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Park
Byung Lae
BL
Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Korea; Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea; Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Cheong
Hyun Sub
HS
Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Korea.
Bae
Joon Seol
JS
Department of Genetic Epidemiology, SNP Genetics, Inc, Seoul, Korea.
Kim
Ji-Hye
JH
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Chang
Hun Soo
HS
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Rhim
TaiYoun
T
Hanyang University, Seoul, Korea.
Park
Jong-Sook
JS
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Jang
An-Soo
AS
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Lee
Young-Mok
YM
Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea.
Kim
Ki-Up
KU
Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea.
Uh
Soo-Taek
ST
Division of Allergy and Respiratory Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea.
Na
Ju Ock
JO
Division of Allergy and Respiratory Medicine, Soonchunhyang University Chunan Hospital, Chunan, Korea.
Kim
Yong-Hoon
YH
Division of Allergy and Respiratory Medicine, Soonchunhyang University Chunan Hospital, Chunan, Korea.
Park
Choon-Sik
CS
Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, Bucheon, Korea. Electronic address: mdcspark@unitel.co.kr.
Shin
Hyoung Doo
HD
Department of Life Science, Sogang University, Seoul, Korea.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D053722:Receptors, Interleukin-17 / Q000235:genetics*; D014158:Transcription, Genetic; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016328:NF-kappa B; D053722:Receptors, Interleukin-17; D048051:p38 Mitogen-Activated Protein Kinases