Background/Purpose: Genetic factors provide over 90% of the susceptibility to ankylosing spondylitis (AS) and recent studies have focused on non-major histocompatibility complex genes. The etiology of uveitis in AS has been suggested to involve two adhesion molecules including intercellular adhesion molecule and leukocyte functional antigen.

Platelet-endothelial cell adhesion molecule 1 (PECAM1), a member of the immunoglobulin superfamily, may be an important regulator of antigen induced cell activation of lymphocytes. The b1 integrin (ITGB1) can associate with different membrane proteins and cause signal transduction by interactions in the extracellular and trans-membrane domain. Therefore, we examined the association of PECAM1 and ITGB1 gene polymorphisms with development of uveitis in patients with AS.

Methods: We conducted a case–control study where 223 AS patients who met the Modified New York criteria and 239 ethnically matched controls were genotyped for 9 single nucleotide polymorphisms (SNPs) in the PECAM-1 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: Conditional logistic regression was used to evaluate the association between the PECAM1 or ITGB1 SNPs with susceptibility to AS, and no significant association was found on both genes. However, in the subgroup analyses between AS patients with uveitis and those without, seven SNPs in PECAM1 gene were associated with the presence of uveitis, including rs1050382 (dominant model (DM), p=0.022), rs2812 (recessive model (RM), p=0.013), rs4968721 (DM, p=0.016), rs6808 (DM, p=0.011), rs6809 (DM, p=0.013), rs9899806 (DM, p=0.013) and rs9913080 (DM, p=0.019) (Table 1). In addition, seven polymorphisms in ITGB1 gene including rs11009147 (DM, p=0.012; co-dominant model (CDM), p=0.034), rs17468 (DM, p=0.012; CDM, p= 0.019), rs2153875 (CDM, p= 0.030), rs2230396 (DM, p=0.012; CDM, p=0.034), rs2488330 (DM, p=0.004; CDM, p=0.017), rs3780871 (DM, p=0.031) and rs7079624 (RM, p=0.004; CDM, p=0.017) were associated with uveitis development (Table 2).

Conclusion: This is the first analysis of the PECAM1 and ITGB1 gene polymorphisms in AS, demonstrating a clear association with uveitis in AS. Given the functional role of PECAM-1 and ITGB1 variants in the immune system, larger studies are now warranted to elucidate the association of PECAM-1 and ITGB1 in the pathogenesis of uveitis in AS.