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, JaeHee Cheon

Research output: Contribution to journalArticle

39 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

Fingerprint

Intestinal Diseases
Behcet Syndrome
Polymorphism
Population
Genotype
Odds Ratio
Confidence Intervals
Genes
Single Nucleotide Polymorphism
Interleukin-23
Interleukin-17
DNA Sequence Analysis
Haplotypes
High performance liquid chromatography
High Pressure Liquid Chromatography
Assays
Nucleotides
Association reactions

All Science Journal Classification (ASJC) codes

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

Cite this

Kim, Eun Soo ; Kim, Seung Won ; Moon, Chang Mo ; Park, Jae Jun ; Kim, Tae Il ; Kim, Won Ho ; Cheon, JaeHee. / Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population. In: Life Sciences. 2012 ; Vol. 90, No. 19-20. pp. 740-746.
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title = "Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population",
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.",
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Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population. / Kim, Eun Soo; Kim, Seung Won; Moon, Chang Mo; Park, Jae Jun; Kim, Tae Il; Kim, Won Ho; Cheon, JaeHee.

In: Life Sciences, Vol. 90, No. 19-20, 22.05.2012, p. 740-746.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population

AU - Kim, Eun Soo

AU - Kim, Seung Won

AU - Moon, Chang Mo

AU - Park, Jae Jun

AU - Kim, Tae Il

AU - Kim, Won Ho

AU - Cheon, JaeHee

PY - 2012/5/22

Y1 - 2012/5/22

N2 - 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.

AB - 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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