Abstract
IntroductionRecent genome-wide and candidate gene association studies in large numbers of systemic lupus erythematosus (SLE) patients have suggested approximately 30 susceptibility genes. These genes are involved in three types of biological processes, including immune complex processing, toll-like receptor function and type I interferon production, and immune signal transduction in lymphocytes, and they may contribute to the pathogenesis of SLE. To better understand the genetic risk factors of SLE, we investigated the associations of seven SLE susceptibility genes in a Chinese population, including FCGR3A, FCGR2A, TNFAIP3, TLR9, TREX1, ETS1 and TNIP1.MethodsA total of 20 SNPs spanning the seven SLE susceptibility genes were genotyped in a sample of 564 unrelated SLE patients and 504 unrelated healthy controls recruited from Yunnan, southwestern China. The associations of SNPs with SLE were assessed by statistical analysis.ResultsFive SNPs in two genes (TNFAIP3 and ETS1) were significantly associated with SLE (corrected P values ranging from 0.03 to 5.5 × 10-7). Through stratified analysis, TNFAIP3 and ETS1 showed significant associations with multiple SLE subphenotypes (such as malar rash, arthritis, hematologic disorder and antinuclear antibody) while TNIP1 just showed relatively weak association with onset age. The associations of the SNPs in the other four genes were not replicated.ConclusionsThe replication analysis indicates that TNFAIP3, ETS1 and TNIP1 are probably common susceptibility genes for SLE in Chinese populations, and they may contribute to the pathogenesis of multiple SLE subphenotypes.
Highlights
Recent genome-wide and candidate gene association studies in large numbers of systemic lupus erythematosus (SLE) patients have suggested approximately 30 susceptibility genes
30 genes have been identified as playing important roles in SLE pathogenesis, and most of these genes have been shown to act in three types of biological processes: immune complex processing, toll-like receptor (TLR) function and type I interferon production, and immune signal transduction in lymphocytes [8,18,21,22]
The single nucleotide polymorphism (SNP) rs11581823 and rs7539036 were selected for FCGR3A; rs10800309, rs4656308 and rs1801274 for FCGR2A; rs5029924, rs5029936, rs5029937, rs2230926 and rs610604 for TNFa-induced protein 3 (TNFAIP3); rs187084, rs352140 and rs352162 for TLR9; rs2242150 and rs3135941 for the 3’ repair exonuclease 1 (TREX1); rs6590330 and rs4937333 for E26 transformation-specific 1 (ETS1); and rs13168551, rs7708392 and rs10036748 for TNFAIP3 interacting protein 1 (TNIP1)
Summary
Recent genome-wide and candidate gene association studies in large numbers of systemic lupus erythematosus (SLE) patients have suggested approximately 30 susceptibility genes These genes are involved in three types of biological processes, including immune complex processing, toll-like receptor function and type I interferon production, and immune signal transduction in lymphocytes, and they may contribute to the pathogenesis of SLE. 30 genes have been identified as playing important roles in SLE pathogenesis, and most of these genes have been shown to act in three types of biological processes: immune complex processing, toll-like receptor (TLR) function and type I interferon production, and immune signal transduction in lymphocytes [8,18,21,22] These findings have revealed many robust associations and the related biological pathways involved in this complex disease. As an unusually heterogeneous disease, the genetic risk factors of SLE are yet to be fully dissected by conducting more studies, especially replications in populations with different ethnic backgrounds
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