Association Study In ETS1 Gene Polymorphism In Systemic Lupus Erythematosus In Yunnan Han Chinese

[Background] Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by the production of broad variety of autoantibodies and subsequent immunecomplex deposition. Various factors have been suggested to contribute to disease pathogenesis including genetic, environment and hormone. Several recent studies have further confirmed that genetic factor plays a critical role in determining the susceptibility and phenotype of SLE. SLE is a polygenic disease which is non-Mendelian inheritance patterns with strong ethnic differences and genetic heterogeneity. In recent years, large number of studies at home and abroad confirmed 30 SLE susceptibility gene. Domestic large sample GWAS had found five new susceptibility genes ETS1, IKZF1, RASGRP3, SLC15A4 and TNIP1 related closely with Hans SLE patients.[Objective] Evaluate the correlation between ETS1 gene polymorphisim and susceptibility and phenotype of SLE in Yunnan Hans using Multiplex SNaPshot technique, to clarify the pathogenesis of SLE.[Methods] Collected 565 Yun Nan hans SLE patients and 501 matched controls; ETS1 gene sequence were amplified using the polymerase chain reaction and ETS1 gene rs4937333, rs6590330 single nucleotide polymorphism were genotyped using Multiplex SNaPshot technique; Statistic was analysed by Plink1.07.[Results] 1. T allele frequencies at the SNPs4937333 was seen in the SLE patients were significantly higher than the controls(p=2.1×10-7); A allele frequencies at the SNPs6590330 was seen in the SLE patients were significantly higher than the controls(p=4.6×10-8).2. There was significant difference of ETS1 gene SNPs4937333 genotype-TT in the case group and control group (p=2.9×10-7); There was significant difference of SNPs6590330 genotype-AA in the case group and control group (p= 4.3×10-8).3. Significant difference was also seen in haploytpe linked inheritance among ETS1 gene rs4937333 and rs6590330, TA haplotype in the case group was significantly higher than the controls(p=1.9×10-7), whilst the CG haplotype in the case group was significantly lower than the controls(p=7.6×10-8).4. The SLE patients were divided into subgroups, there were significant differences in T allele frequencies at the SNPs4937333 and A allele frequencies at the SNPs6590330 of malar rash, discoid rash, photosensitivity, arthritis, serositis, kidney damage, hematologic disorder, immunologic disorder and ANA Positive. In A allele frequencies at the SNP rs6590330:malar rash(p=5.5×10-7), photosensitivity(p=0.0027), arthritis (p=8.9×10-6), serositis(p=6.1×10-4), kidney damage(p=7.2×10-6), hematologic disorder(p=2.3×10-7), immunologic disorder(p=1.9×10-7) and ANA Positive(p= 2.9×10-7); In T allele frequencies at the SNPs4937333, malar rash(p= 8.1×10-7,) discoid rash(p= 0.0447), photosensitivity(p= 9.4×10-5), arthritis(p= 4.7×10-6) serositis(p=2.8×10-3), kidney damage(p=5.9×10-6), hematologic disorder (p=1.2×10-6), immunologic disorder(p=2.1×10-7) and ANA Positive (p=1.1×10-6)[Conclusion] 1. Polymorphisim at rs4937333 and rs6590330 of ETS1 gene have susceptibility for Yun Nan han SLE patients.2. rs4937333-T and rs6590330-A allele of ETS1 gene increase the risk of malar rash, photosensitivity, arthritis, serositis, kidney damage, hematologic disorder, immunologic disorder and ANA Positive, rs6590330-A also increase the risk of discoid rash.