Genotype-phenotype Analysis Between Two SNPs Rs1913517 And Rs463426 With Clinical Features Of Systemic Lupus Erythematosus In Chinese Han Population

Background Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease influenced by genetic and environmental factors. In 2008, recent four genome-wide association studies (GWAS) of SLE in European populations have identified more than twenty robust susceptibility genes and/or loci. We have discovered 9 novel susceptibility loci and confirmed 7 previously reported ones for SLE in a recent GWAS of Chinese Han population including 10q11.22 ( SNP rs1913517) and 22q11.21 (SNP rs463426).Several genotype-phenotype analyses of SLE have been demonstrated and revealed that the complexity of SLE with the feature of extremely heterogeneity, which might give a new insight into the etiology and pathogenesis of SLE.Objective? ? To investigate the association between clinical features of SLE(malar rash, discoid rash, renal disorder, hematologic disorder,neurologic disorder,oral ulcers, photosensitivity , serositis, arthritis, vasculitis or multiple autoantibodies in terms of antinuclear antibody (ANA), antibody to native DNA in abnormal titer (Anti-DNA) and antibody to Sm nuclear antigen (Anti-Sm)) and SNPs rs1913517 at 10q11.22 and rs463426 at 22q11.21 in Chinese Han population, revealed that the complexity pathogenesis of SLE, and help to further elucidate disease mechanisms and seek better clinical cure.Methods Subphenotyes were analyzed according to the ACR classification criteria for SLE and age onset. We performed case-only analyses (e.g. presence of Malar rash versus no Malar rash) to explore the relationship of the novel SNPs with subphenotypes of SLE, and performed case–control analyses (e.g. presence of Malar rash versus healthy controls) to examine the risk conferred by the two SNPs on different subtypes of SLE. P values, odds ratios (ORs) with 95%CI were calculated using SPSS10.0. P values<0.05 were regarded as significance.Results? ? In phenotype case-only analyses, the SNP rs1913517 showed significant difference between Anti-Sm (+) and Anti-Sm (-) (OR=0.83, 95% CI: 0.74–0.93, p=0.0015). In case–control analyses, SNP rs1913517 showed an association only in patients without Neurologic disorder, Serositis and Anti-Sm, but not in the presence of Neurologic disorder ,Serositis and Anti-Sm (p>0.05).The allele frequency of rs463426 was no significantly different in all subphenotypes in case-only, but subphenotype-control analyses showed that the rs463426 was significantly associated in all subphenotypes and controls.Conclusion The results indicate that 10q11.22 (rs1913517) was associated with Anti-Sm of SLE.22q11.21(rs463426) having stronger genetic effect on SLE susceptibility, but it might not be associated with a certain phenotype of SLE.