title: Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Kim
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Chang Mo
authors.initials: CM
authors.lastname: Moon
authors.forename: Jae Jun
authors.initials: JJ
authors.lastname: Park
authors.forename: Tae Il
authors.initials: TI
authors.lastname: Kim
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001528:Behcet Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D007410:Intestinal Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D012306:Risk; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D050797:STAT4 Transcription Factor