Chinese Han Population C1qa The Ikzf1 Single Nucleotide Polymorphisms And Systemic Lupus Erythematosus-related Research

[Abstract] Background systemic lupus erythematosus(SLE) is a systemic autoimmune disease characterized by the breakdown of immunotolerance and the production of a wide range of autoantibodies that target multiple tissues and organs. Lupus nephritis (LN) is one of the common and serious complications in SLE. Both genetic and enviromental factors contributed to the diease pathogenesis. Complement played an important role in the initiation of inflammation and clearance of immune complexs. C1q was one of the major components of the classical pathway of complement activation, and variants of C1q gene can lead to immune system disorder and autoimmunity. IKZF1 was a hemopoietic-specific zinc finger protein. This gene can fuction as a regulator of immune cell differentiation and proliferation, and mouse model studies illustrated that IKZF1-null mice showed disrupted progression of T and B cell development. However, less association studies of this gene polymorphisms with SLE were conducted. Objective This study intended to investigate the association of the single nucleotide polymorphisms (rs172378 and rs665691 in C1q, rs4917014 in IKZF1) with SLE and LN, as well as subphenotypes of SLE in Chinese Han population. Methods 748 SLE patients (including 456 patients with LN) and 750 healthy controls were recruited, and all the subjects were unrelated Chinese Hans. The selected polymorphisms were genotyped by the MassArray system (Sequenom, San Diego, CA). Results The distributions of allele, genotype and haplotype frequencies of C1q gene polymorphisms did not exhibit significant difference between SLE patients and controls (p>0.05), and the same trends were obtained in the analyses based on different genetic models (additive, dominant and recessive), the female group and subphenotype groups. C1qA (rs 172378) allele frequency of LN patients between anti-Sm antibody positive and negative had Statistical difference (p=0.046, OR=1.43,95%CI=1.01-2.03), but the difference was not significant. On the other hand, rs4917014 achieved positive association in all analyses except the subphenotype analyses. We detected no association between rs4917014 and subphenotypes of SLE or LN. T allele (rs4917014) was the risk allele (p=2.43×10-6, OR=1.47,95%CI=1.25-1.73), and the frequency of T allele differed significantly between cases and controls (cases:controls=74.8%:67.0%). Conclusions rs172378 and rs665691 were not susceptibility loci for SLE and LN. Nevertheless the SNP of rs4917014 was validated to be strongly associated with SLE in Chinese Han population, but it was not risk for LN or other clinical manifestations.