Identification Of Susceptibility SNPs In CTLA4 And PTPN22 For Scleritis In Han Chinese

Backgrounds and AimsScleritis is a group of heterogeneous ocular disorders characterized by chronic inflammation of the sclera.The inflammation primarily affects the sclera,and scleritis can be clinically divided into anterior scleritis,posterior scleritis,and pan-scleritis based on the location of the inflammation.Scleritis is associated with a variety of systemic autoimmune diseases and vasculitis.Although the pathogenesis of scleritis is not well understood,it has been proposed that T cell mediated immunity and immune complex deposition are involved in its pathogenesis.The gene of cytotoxic T lymphocyte-associated antigen-4(CTLA4),a negative regulator of T cells,Protein tyrosine phosphatase nonreceptor type 22(PTPN22)also serves as a negative factor on TCR signaling.It has been reported that both CTLA4 and PTPN22 play important roles in autoimmune responses.A number of studies have shown that several SNPs of CTLA4 and PTPN22 are associated with a numberof systemic autoimmune diseases.In view of the important effects of CTLA4 and PTPN22 on the immune response and their strong association with susceptibility to a number of autoimmune diseases,we performed this study to evaluate the association of 13 tag SNPs of CTLA4 and PTPN22 with scleritis in a Chinese Han population.Materials and MethodsThis study included 432 scleritis patients and 710 healthy controls,Four tag SNPs of CTLA4(rs733618,rs5742909,rs231775 and rs3087243)and 9 tag SNPs of PTPN22(rs3789604,rs150426536,rs1746853,rs1217403,rs1217406,rs3789609,rs1217414,rs3789612,rs2488457)were selected using Haploview.Genotyping was performed with the Sequenom MassArray(?)iPLEX GOLD Assay.Genotype and allele frequency differences were analyzed by Chi-square test and Bonferroni correction.Haplotype analysis was performed to further evaluate the association of these two genes with scleritis.ResultsCTLA4/rs3087243 G allele frequency and GG genotype frequency were significantly increased in scleritis patients as compared to healthy controls(corrected P value[Pe]=0.02,odds ratio[OR]=1.475;Pc=0.04,OR=1,546,respectively).None of the tested SNPs in the PTPN22 gene showed an association with scleritis.Haplotype analysis revealed a lower frequency of a CTLA4 TCAA haplotype(order of SNPs:rs733618,rs5742909,rs231775,rs3087243)(Pc=4.26×10-3,OR=0.618)and a higher frequency of a PTPN22 TTATACGCG haplotype(order of SNPs:rs3789604,rs150426536,rs1746853,rs1217403,rs1217406,rs3789609,rs1217414,rs3789612,rs2488457)(Pc=2.83×10-4,OR=1.457)in scleritis patients when compared to healthy controls.ConclusionsOur findings indicate that CTLA4 and PTPN22 might confer genetic susceptibility to scleritis in a Chinese Han population.