Journal
LIFE SCIENCES
Volume 90, Issue 19-20, Pages 740-746Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.03.017
Keywords
Behcet's disease; IL17A; IL23R; STAT4; Polymorphism
Funding
- Korea Research Foundation
- Korean Government (MOEHRD) [KRF-2008-331-E00105]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A080588]
- Ministry of Health and Welfare, Republic of Korea [A084943]
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2009-0069149]
- Korea Health Promotion Institute [A084943] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2009-0069149] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 TagMan genotyping assays. Key findings: Individual polymorphism analysis revealed that the TT genotype of IL17A rs8193036 (odds ratio (OR) 2.10, 95% confidence interval (Cl) (1.12-3.92), p = 0.021), and GG + GT genotype of IL23R rs1884444 (OR 1.92, 95% Cl (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% Cl (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. (C) 2012 Elsevier Inc. All rights reserved.
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