Association Study On Single-nucleotide Polymorphisms Of Irf3 Gene And Environmental Factors With Systemic Lupus Erythematosus In Chinese Han Population

Objective Increasing evidences indicate that the activated type I IFN system in systemic lupus erythematosus (SLE) is critical in the etiopathogenesis of the disease and is an important therapeutic target. The aim of this study was to investigate the role of interferon regulatory factor (IRF) 3 gene, a kind of interferon regulatory factor, in susceptibility to SLE using family-based association methods,and to analyze the influences of interaction of many environmental factors and gene-enviromental on systemic lupus erythematosus.Methods We studied three SNPs (rs2304204, rs2304206, and rs7251) in the IRF3 gene with respect to genetic susceptibility to SLE. Samples were genotyped for IRF3 SNPs using TaqMan method. A total of 171 patients aged from 12 to 63 years, were enrolled according to 1997 criteria of American College of Rheumatology (ACR), 329 family members of these patients were also included. Genotyping was performed by Taqman Assay. Family-based association analysis was performed to explore the association between gene polymorphism and SLE. The possible environmental risk factors and the possible interactions between gene and environment on SLE were analyzed using Case-control study within the family. To estimate the bias of the Case-control study within the family, Case-control study was carried out to further analysis of environmental risk factors.Results One hundred and seventy-one patients were classified by rs2304204, rs2304206 and rs7251 genotypes. The frequencies of rs2304204 AA, AG and GG genotypes were 32.2%, 55.6% and 12.3%, respectively. The A and G allele frequencies were 59.9% and 40.1%, respectively. The frequencies of rs2304206 CC, CT and TT genotypes were 29.2%, 67.3% and 3.5%, respectively. The C and T allele frequencies were 62.9% and 37.1%, respectively. The frequencies of rs7251 CC, CG and GG genotypes were 11.7%, 64.3% and 24.0%, respectively. The C and G allele frequencies were 43.9% and 56.1%, respectively. Univariate (single-marker) family-based association tests (FBATs) demonstrated that the T allele at position of rs2304206 was significantly associated with the susceptibility to SLE in a dominant model (Z =2.238, P =0.025). Genotype analysis showed that the heterozygote of rs2304206 and rs7251 had greater susceptibility to SLE (rs2304206, CT, Z =3.107, P =0.001; rs7251, CG, Z=2.407, P=0.016). The univariate conditional Logistic regression model (α=0.20) showed that some enviromental factors were significant between the SLE cases and their normal siblings, such as sex[P=0.048, OR=0.357],noise[P=0.026,OR=3.54],hypersensitiveness[P=0.006,OR=5.667],Infection[P=0.017, OR=65.289]; Multi-conditional Logistic regression model showed that there have possible interaction of hypersensitiveness*rs2304206 [P=0.038,OR=5.000] and Infection*rs2304206 [P=0.042,OR=65.289], it showed that the rs2304206 of IRF3 gene may not be the independent risk factor. And the results of case-control study showed that several environmental risk factors are related to systemic lupus erythematosus.Conclusions Our study suggests that a SNP (rs2304206) in intro 1 region of IRF3 gene may be a susceptibility factor for SLE in the Chinese Han population. Many environmental risk factors are related to systemic lupus erythematosus, and rs2304206 gene polymorphism increase the risk of persons with hypersensitiveness or infection to development of systemic lupus erythematosus.