The Screening And Verification Research Of Non-HLA Susceptibility Genes Of Ankylosing Spondylitis-associated Uveitis

Objective Uveitis is considered the most frequent extra-articular manifestation of Ankylosing Spondylitis（AS）.And it can cause impaired vision and even blindness.But the pathogenesis of it is not clear,current studies found that genetic factors play an important role in it.Past studies reported that genes in HLA region and the occurrence of AS-associated uveitis strongly correlate.A large number of research suggest that non-HLA region may still exist other susceptibility genes.In this study,we investigated non-HLA susceptibility genes of AS concomitant with uveitis in a Chinese population.Methods First,9p21-24 was selected as the region of susceptibility genes.Second,several candidate genes were selected from this region by bioinformatics analysis.Thirdly,a two-stage case control study was used to verify these candidate genes.The first stage included50 AS with uveitis,50 AS without uveitis,and 145 healthy controls.The PCR+direct sequencing and cloning sequencing were used to identify SNPs in this stage.The second stage included 245 AS with uveitis,360 AS without uveitis and 530 healthy controls.Results IFNA1,IFNB1,IFNA8,and IFNA13 were selected as candidate genes by means of a series of bioinformatics analysis.In the first stage,it was found that the frequency of IFNA1 rs28383797（G allele）and IFNA13 rs653778（T allele）in AS with uveitis was higher than that in AS without uveitis and healthy controls.In the second stage,more samples were used to verify the two single nucleotide polymorphisms.After comprehensive data analysis in the two stages,the frequency of rs28383797 G allele and rs653778 T allele in AS with uveitis was significantly higher than that in AS without uveitis(P=1.9×10^-7,OR=2.161,95%CI=1.609-2.902 and P=1.5×10^-9,OR=2.028,95%CI=1.610-2.554)and healthy controls(P=2.4×10^-12,OR=2.602,95%CI=1.978-3.42;P=4.6×10^-18,OR=2.52,95%CI=2.038-3.117).Conclusion Rs28383797（G allele）of IFNA1 and rs653778（T allele）of IFNA13were associated with AS concomitant uveitis,and may act as the non-HLA region susceptibility genes of AS with uveitis in the Chinese population.