TNIP1,SLC15A4 And RasGRP3 Are Associated With Clinical Features Of Systemic Lupus Erythematosus In Chinese Han Population

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations influenced by genetic and environmental factors. We have identified five novel susceptibility genes including TNIP1, SLC15A4 and RasGRP3 for SLE in a recent genome-wide association study (GWAS) of Chinese Han population.Objective Here we investigated their relationships of the three novel susceptibility genes with disease subphenotypes, including renal nephritis, photosensitivity, ANA, age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arithritis and vasculitis to further clarify the pathogenesis of systemic lupus erythematosus, and bring hope to develope new treatments of etiologyMethods We first performed case-only analyses (e.g. presence of photosensitivity versus no photosensitivity) to identify which subphenotypes were associated with the specific SNPs. Then we performed subphenotype-control analyses (e.g. presence of photosensitivity or negative of photosensitivity versus health controls) to examine the risk conferred by the 5 SNPs on different subtypes of SLE. We correlated the presence of risk alleles with total number of ACR criteria, age at diagnosis and vasculitis of SLE. P values, odd ratios (ORs) and 95% confidence interval (CI) were estimated using PLINK 1.06 software,13 and P values below 0.05 were considered to be statistically significant.Results Significant associations were found for SNP rs10036748 of TNIP1 with photosensitivity (OR = 0.87, P = 0.01) and vasculitis (OR = 1.18, P = 0.04); rs10847697 of SLC15A4 with discoid rash (OR = 1.18, P = 0.02); rs13385731 of RasGRP3 with malar rash (OR = 1.20, P = 0.01), discoid rash (OR = 0.78, P = 0.02) and ANA (OR = 0.72, P = 0.004);Conclusions Our study suggested that these susceptibility genes might not only play important roles in the development of SLE in Chinese Han population, but also SNP rs10036748 of TNIP1 may be associated with photosensitivity and vasculitis , rs10847697 of SLC15A4 may be associated with discoid rash, rs13385731 of RasGRP3 may be associated with malar rash, discoid rash and ANA.