Study Of The Association Of IL-10Gene Polymorphisms With Susceptibility To Behcet’s Disease And Vogt-Koyanagi-Harada Syndrome

Purpose: Behcet’s disease (BD) and Vogt-Koyanagi-Harada syndrome (VKH) are themost common and severe sight-threatening uveitis entities in China. This study wasaimed to investigate the association of IL-10gene polymorphisms with BDandVKHsyndrome in Chinese Han.Methods: A two-stage association and gene expression study was performed in718BD patients,300VKH patients, and1753controls.Genotyping of the IL-10gene wasperformed for six single nucleotide polymorphisms (SNPs), including rs1800871,rs1800872, rs1800896, rs3021094, rs3790622, and rs1554286using polymerase chainreaction–restricted fragment length polymorphism or TaqMan SNP assays. Real-timePCR was performed to test the IL-10mRNA expression of the associatedpolymorphism.Allele and genotype frequencies werecompared between patients andcontrols by Chi-square test using SPSS(version16.0；SPSS Inc．，Chicago，IL，USA)．The linkage disequilibrium between alleles and various haplotypes wasconstructed using theSHEsis network platform (http://analysis.bio-x.cn). The P-valueswere corrected (Pcorrected) with the Bonferroni correction by multiplying with thenumber of analyses performed．The Pcorrected＜0.05was considered as significant．Results: All genotype distributions in healthy controls were inHardy–Weinbergequilibrium.The first-stage result showed increased frequencies of the rs1800871TT genetype,rs1800872AAgenetype and rs1554286TTgenetype (Pcorrected(Pc)=5.03×10-3,OR=1.778; Pc=4×10-4, OR=1.962; Pc=2.72×10-5, OR=2.154,respectively) andsignificantly descended frequencies of the rs1800871, rs1800872and rs1554286C allele (Pc=1.82×10-5, OR=0.544; Pc=6.1×10-5, OR=0.562; Pc=3.15×10-5,OR=0.558,respectively） in BD patients compared with controls. There was noassociation of the tested six SNPs with VKH syndrome. Compared to the controls,there was no association of the tested six SNPs with VKH syndromewith extraocularfindingsincludingheadache, tinnitus, hair loss or hair, vitiligo.A second-stage study was therefore performed in BD patients to validate the result ofthe first stage and showed a significantly increased frequency of the rs1800871TTgenetype (Second stage Pc=2.33×10-4, OR=1.619; Combined data；Pc=2.50×10-8,OR=1.713) and a significantly descended frequencies of the rs1800871, rs1800872and rs1554286C allele(Second stage Pc=5.59×10-5, OR=0.670; Combined data；Pc=3.65×10-11, OR=0.613). Compared to the controls, an increased frequency of thers1800871T allele was observed in BD patients with extraocular findings, includinggenital ulcer, skin lesions and in those with a positive pathergy test.No difference was found for the mRNA expression of IL-10in peripheral bloodmononuclear cells (PBMCs) of controls with different genotypes of rs1800871afterstimulation of lipopolysaccharide (LPS) or anti-CD3/CD28antibodies.Conclusions: rs1800871， rs1800872and rs1554286of IL-10gene areassociatedwithsusceptibility to BD. IL-10gene polymorphismis not associated withsusceptibility to VKH syndrome in the Chinese Han population.