Presentation: The Foxo3a Gene Polymorphism is Associated with Ankylosing Spondylitis (2007)

822 The Foxo3a Gene Polymorphism is Associated with Ankylosing Spondylitis

The overall contribution of HLA-B27 to Ankylosing spondylitis(AS) susceptibility is less than 40%. Recently, genome wide linkage studies showed the strongest evidence at the MHC and 6q where Foxo3a gene was mapped (6q21). Foxo3a is a recently discovered member of the family of forkhead transcription factors, which is a regulator of immune cell homeostasis. Foxo3a-deficient mice are resistant to neutrophilic inflammation and immune complex-mediated inflammatory arthritis. Active Foxo3a can protect cells from oxidative stress, and stress signals including oxidative stress and TNF-α stimulation oppose inactivation of Foxo proteins. Furthermore, TNF-α and IL-1, which have a crucial role in AS, did not induce apoptosis in wild-type, but markedly induce apoptosis in Foxo3a deficient mice.
Purpose: We examined whether Foxo3a gene polymorphisms are associated with susceptibility to AS.
Methods: Genomic DNA was isolated from 223 Korean patients with AS who met the Modified New York criteria and 239 ethnically matched controls. Genotyping was conducted for 6 single nucleotide polymorphisms (SNPs) in the Foxo3a promoter and gene. Genomic DNA was isolated from peripheral blood leukocytes by a standard phenol-chloroform method and a GoldenGate assay (Illumina, http://www.illumina.com) was used for genotyping.
Results: We observed a significant association between the SNP at rs2802290 with susceptibility to AS. The genotype of rs2802290 showed a decreased risk of AS with a recessive genetic model (OR=0.361, 95%CI=0.14-0.933, p=0.035). Haplotype was further analyzed, however, it did not show any significant difference.
Conclusion: This is the first analysis of the Foxo3a gene polymorphisms in AS, demonstrating an association with susceptibility to AS. Given the functional role of Foxo3a variants in the immune system and apoptosis, larger studies are now warranted to elucidate the association of Foxo3a in the pathogenesis of AS.

  S. Shim, Korea Health 21 R&D Project(01-PJ3-PG6-01GN09-003), 2; D. Sheen, None; M. Lim, None; J. Hur, None; Y. Joo, None; S. Chae, None; H. Chung, None; T. Kim, None.