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

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48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)740-746
Number of pages7
JournalLife Sciences
Volume90
Issue number19-20
DOIs
Publication statusPublished - 2012 May 22

Bibliographical note

Funding Information:
This research was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund ) ( KRF-2008-331-E00105 ), a grant from the Korea Healthcare Technology R&D Project ( A080588 ), the Ministry for Health, Welfare & Family Affairs, Republic of Korea , a grant from the 2009 Good Health R&D Project, Ministry of Health and Welfare, Republic of Korea ( A084943 ), and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number 2009-0069149 ).

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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