Study On The Association Of CARD9 Gene Polymorphisms With Behcet Disease And Acute Anterior Uveitis In Chinese Han Population

Backgrounds and AimsCaspase recruitment domain-containing protein 9(CARD9)gene plays an important role in innate immune responses.Recent genome-wide association studies(GWAS)and candidate gene studies of single nucleotide polymorphisms(SNP)have shown that CARD9 gene polymorphisms predispose to a number of autoimmune and autoinflammatory disorders in humans.Intriguingly,two recent studies on experimental autoimmune uveoretinitis(EAU)have revealed that CARD9-mediated responses play an early initiating role in the development of autoimmune uveitis.Behcet disease(BD)is an important type of blinding eye disease in uveitis.Most patients develop in young adults,involving multiple systems,and are prone to recurrent attacks and difficult treatment.Acute anterior uveitis(AAU)is the most common type of uveitis worldwide.Although the exact pathogenesis of uveitis is unclear,more and more studies have shown that complex genetic backgrounds andabnormal immune responses may be associated with the development of uveitis.The present study was therefore undertaken to examine whether polymorphisms of CARD9 gene were associated with BD and AAU in a Chinese Han population.Material and MethodsBD patients and AAU patients were selected as case groups,and healthy individuals as control group.A total of 480 BD patients,1151 AAU patients and 1440 healthy controls were enrolled in this study.Genotyping of the CARD9 gene was performed for 6 SNPs,including rs4077515,rs11145769,rs9411205,rs4073153,rs59902911 and rs1135314,using iPLEX Gold genotyping assay.Genotype and allele frequencies between cases and healthy controls were analyzed using χ2 test,and P values in multiple comparisons were adjusted by Bonferroni correction.Haplotype analysis was examined in the 5 SNPs between cases and healthy controls.ResultsAfter correction by Bonferroni,there was no significant difference in the genotype and allele frequency of 6 SNP sites in CARD9 gene between BD group and healthy control group,AAU group and healthy control group.Gender stratification also found no significant difference between the case group and the control group.According to the stratification analysis of BD extraocular manifestations,according to the stratification analysis of whether AAU is associated with ankylosing spondylitis or HLA-B27 phenotype,there is no significant difference between the 6SNP sites in the case group and the control group.Haplotype analysis for CARD9 gene showed a significant association with the CGCCA haplotype in BD(Pc=0.012,OR=0.585,95%CI= 0.409~0.837).ConclusionsThis study shows that a five-SNP haplotype of the CARD9 gene(CGCCA)may be a protective factor for BD,but not for AAU.