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Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population.

 Eun Soo Kim  ;  Seung Won Kim  ;  Chang Mo Moon  ;  Jae Jun Park  ;  Tae Il Kim  ;  Won Ho Kim  ;  Jae Hee Cheon 
 LIFE SCIENCES, Vol.90(19-20) : 740-746, 2012 
Journal Title
Issue Date
Adult ; Asian Continental Ancestry Group/genetics ; Behcet Syndrome/epidemiology ; Behcet Syndrome/genetics* ; Behcet Syndrome/pathology ; Female ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study ; Haplotypes ; Humans ; Interleukin-17/genetics* ; Intestinal Diseases/epidemiology ; Intestinal Diseases/genetics* ; Intestinal Diseases/pathology ; Korea/epidemiology ; Male ; Middle Aged ; Nucleic Acid Amplification Techniques ; Phenotype ; Polymorphism, Genetic/genetics ; Polymorphism, Single Nucleotide ; Receptors, Interleukin/genetics* ; Risk ; STAT4 Transcription Factor/genetics*
Behcet's disease ; IL17A ; IL23R ; STAT4 ; Polymorphism
AIMS: Although polymorphisms in IL23R have recently been proposed to predispose to Behcet's disease (BD), associations between IL23R polymorphisms and intestinal BD have yet to be elucidated. We therefore performed a study to evaluate whether IL17A, IL23R, and STAT4 polymorphisms are associated with susceptibility to intestinal BD in the Korean population. MAIN METHODS: Single nucleotide polymorphisms (SNP) in the IL17A, IL23R, and STAT4 genes were analyzed using DNA sequencing, denaturing high performance liquid chromatography, and TaqMan genotyping assays. KEY FINDINGS: Individual polymorphism analysis revealed that the TT genotype of IL17A rs8193036 (odds ratio (OR) 2.10, 95% confidence interval (CI) (1.12-3.92), p=0.021), and GG+GT genotype of IL23R rs1884444 (OR 1.92, 95% CI (1.03-3.57), p=0.034) was associated with the development of intestinal BD. When these two genotypes were combined, the risk of BD increased compared to that of patients with no-risk or one-risk genotype (OR 2.21, 95% CI (1.13-4.34), p=0.021). Furthermore, statistically significant gene-gene interactions were observed between G149R in IL23R vs. rs11685878 in STAT4, rs2275913 in IL17A vs. rs7574865 in STAT4, and rs11889341 in STAT4 vs. rs2275913 in IL17A. The haplotypes of IL17A had a positive association with intestinal BD risks, whereas those of IL23R were protective for disease development. SIGNIFICANCE: Our results indicate that the interaction of specific IL17A, IL23R, and STAT4 SNPs modulate susceptibility to intestinal BD in the Korean population, suggesting that the IL-17/23 axis plays a significant role in disease pathogenesis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Eun Soo(김은수)
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Moon, Chang Mo(문창모)
Park, Jae Jun(박재준)
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
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