The Association Of Polymorphisms Of ERAP1/ERAP2/RUNX3 And The Susceptibility Of Ankylosing Spondylitis And Acute Anterior Uveitis In Chinese Han

Background:There are two main types of acute anterior uveitis(AAU),the one is idiopathic acute anterior uveitis(IAAU)and the other is anterior uveitis with ankylosing spondylitis(AS).In patients with AS,the incidence of AAU will continue to increase.Previous studies showed that ERAP1/ERAP2 and RUNX3 genes polymorphisms are associated with AS and(or)AAU in European Caucasians.The combined risk of ERAP1/ERAP2 and HLA-B27 in AS is up to 70%in European populations.RUNX3 and ERAP1/ERAP2 play an important role in the development,differentiation and function of T cells.Both AS and AAU are considered as T cell mediated autoimmune diseases.The susceptibility of ERAP1 gene to AS has been deeply studied in European Caucasians.However,contradictory results were reported in Chinese Han.Objective:Purpose of this study was to determine whether 11 candidate SNPs in ERAP1/ERAP2 and 6 in RUNX3 genes confer susceptibility to AS and AAU in Chinese Han.The differences in the association of ERAP1,ERAP2 andRUNX3 gene polymorphisms with AS disease in European Caucasians and Asians were reassessed through literature analysis.Methods:Seventeen candidate SNPs were selected(eleven in or near ERAP1/ERAP2 gene and six in RUNX3 gene),based on reported susceptibility loci in ERAP1/ERAP2 and RUNX3 as identified in GWAS results in European Caucasians and replicated in Asian patients,including novel loci identified in Asian populations.A case-control association study was performed in 882 AS,884 AS+AAU+,384 AAU patients and 1727 healthy controls.Genomic DNA was collected from peripheral whole venous blood of healthy individuals and patients.iPLEX Gold Genotyping Assay technique was used for genotyping analysis on a Sequenom MassArray System.Allele and genotype frequency were calculated with the Sequenom MassArray System platform.The Bonferroni correction was employed to correct multiple comparisons.A corrected p value(Pc)of less than 0.05 was considered to be statistically significant.A meta-analysis was performed,based on PubMed database,to assess the association of polymorphisms of ERAP1 with AS susceptibility in Asian and Europe population.Revman5.2 software was applied for the Meta-analysis.Results:No association was found between 17 candidate SNPs of ERAP1/ERAP2/RUNX3 and susceptibility of AS+AAU+,AS and AAU patients in Chinese Han.A case-control study between patients with HLA-B27 positive and non-typed healthy controls also failed to demonstrate an association of the tested SNPs with AS+AAU+,AS and AAU patients.Moreover,a meta-analysis showed that there was no association of rs30187,rs27037,rs27980,rs27434 and rs27582 in ERAP1 with AS in Chinese Han.The meta-analysis showed strong association of rs30187,rs27434 and rs27044 in ERAP1 with AS susceptibility in European descendantsConclusion:17 SNPs in ERAP1/ERAP2 and RUNX3 genes did not confer disease susceptibility to AS in Chinese Han and similar results were found in AS+AAU+patients and AAU patients.