Multiple lines of evidence have shown that systemic lupus erythematosus (SLE) is attributable to both genetic and environmental factors. The product of GRB2 is a key factor in the activation of B cells and has been reported to be significantly associated with SLE in European populations. In the study, we aimed to investigate the relationship between GRB2 and SLE. A total of 1,710 Han Chinese women comprising 567 SLE patients and 1,143 controls were recruited to genotype 20 selected tagging SNPs. We tested the potential association between 13 clinical variables of SLE and the significant polymorphisms related to SLE. The eQTL data were extracted from the GTEx database to examine the functional consequences of the targeted SNPs. A significant association signal was identified between rs36023980 and SLE in both genotypic and allelic analyses (OR = 0.61, P = 0.0003). Complement inhibition was shown to be significantly associated with the genotypes of SNP rs36023980 in SLE patients (P_genotype = 0.003). Further stratification analyses showed that the genetic association signal of SNP rs36023980 on SLE could only be identified in cases with complement inhibition. SNP rs36023980 was also identified to be significantly associated with the expression of GRB2 in whole blood and sun-exposed skin. In conclusion, our findings confirm the results from the previous GWAS and are the first to report the association of GRB2 with SLE in Han Chinese population.

多条证据表明，系统性红斑狼疮（SLE）可归因于遗传和环境因素。GRB2的产物是B细胞活化的关键因素，据报道与欧洲人群的SLE密切相关。在研究中，我们旨在研究GRB2之间的关系。和SLE。招募了总共1,710名汉族女性，包括567名SLE患者和1,143名对照，以对20种选定的标记SNPs进行基因型分析。我们测试了SLE的13个临床变量与与SLE相关的显着多态性之间的潜在关联。从GTEx数据库中提取了eQTL数据，以检查目标SNP的功能后果。在基因型和等位基因分析中，rs36023980和SLE之间均发现了显着的关联信号（OR = 0.61，P  = 0.0003）。已显示补体抑制与SLE患者SNP rs36023980的基因型显着相关（P_基因型 = 0.003）。进一步的分层分析表明，SNP rs36023980在SLE上的遗传关联信号只能在具有补体抑制作用的情况下才能识别。SNP rs36023980也被确定与GRB2在全血和日晒皮肤中的表达显着相关。总之，我们的发现证实了先前GWAS的结果，并且是第一个报告GRB2与SLE在汉族人群中的关联的结果。