title: Association of IL-12B genetic polymorphism with the susceptibility and disease severity of ankylosing spondylitis.
abstract: OBJECTIVE
  Interleukin 23 (IL-23) stimulates the differentiation of T helper 17 (Th17) cells, which are involved in the pathogenesis of ankylosing spondylitis (AS). Binding of IL-23 to the IL-23 receptor complex activates Janus kinases 2 and tyrosine kinase 2, which phosphorylate IL-23R and subsequently promote the transcription of the IL-17 gene. IL-12B encodes a p40 subunit common to IL-12 and IL-23. We evaluated the effects of IL-12B and IL-23R genotype on the occurrence and clinical features of AS.
  
  
  METHODS
  A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Genotypes of IL-12B A1188C (rs3212227) and IL-23R C2370A (rs10889677) were identified by polymerase chain reaction/restriction fragment-length polymorphism. Disease activity and functional status were assessed by Bath AS indices.
  
  
  RESULTS
  Subjects carrying IL-12B CC [matched relative risk (RR(m)) 1.93, 95% CI 1.23-3.03] and IL-12B AC (RR(m) 1.73, 95% CI 1.21-2.46) genotypes had a significantly greater risk of developing AS than subjects with the IL-12B AA genotype. Subjects carrying both IL-12B CC and IL-23R AA genotypes also had a significantly higher risk (RR(m) 2.98, 95% CI 1.51-5.89) of developing AS compared to those with IL-12B AA and IL-23R CC/CA genotypes, and this interaction between IL-12B and IL-23R was significant. Patients with AS who had IL-12B CC and IL-12B AC genotypes had an obviously increased Bath Ankylosing Spondylitis Disease Activity Index score compared to those who carried the IL-12B AA genotype (4.3 vs 3.7).
  
  
  CONCLUSIONS
  The IL-12B A1188C genotype was associated with the development and disease severity of AS.
authors: Institute of Medicine, Chung Shan Medical University, No. 110 Chien-Kuo N Road, Section 1, Taichung 40201, Taiwan.
authors: Ruey-Hong
authors: RH
authors: Wong
authors: James Cheng-Chung
authors: JC
authors: Wei
authors: Chun-Huang
authors: CH
authors: Huang
authors: Hong-Shen
authors: HS
authors: Lee
authors: Shang-Yan
authors: SY
authors: Chiou
authors: Shin-Hua
authors: SH
authors: Lin
authors: Yan-Wei
authors: YW
authors: Cai
authors: Pei-Hsuan
authors: PH
authors: Hung
authors: Ming-Fuu
authors: MF
authors: Wang
authors: Shun-Fa
authors: SF
authors: Yang
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000503:physiopathology*
chemical_list: C500879:IL12B protein, human; C515500:IL23R protein, human; D053762:Interleukin-12 Subunit p40; D018123:Receptors, Interleukin