To the Editor: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic components, with over 40 susceptibility loci identified at present. These SLE susceptibility loci are predominantly common variants that have been confirmed among multiple ancestries, suggesting shared mechanisms in disease etiology1. However, genetic heterogeneity was also suggested, as some genetic polymorphisms are restricted to specific ethnic populations. Recent descriptions of gene–gene interactions, or epistasis, may explain some of the genetic heterogeneity and missing heritability in SLE. We previously reported potential epistasis between BLK and TNFSF4 in both Chinese and white populations, suggesting that unbalanced functions of B cell and T cell signaling may be involved synergistically in the pathogenesis of SLE2. Another large-scale association study confirmed the genetic interactions between BANK1 and BLK in Europeans, indicating B cell activity and a B cell-specific pathway were crucial in lupus pathogenesis3. No further replications were conducted in Chinese subjects or other populations with independent sets of cases … Address correspondence to Prof. H. Zhang, Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, China. E-mail: hongzh{at}bjmu.edu.cn
