Higher DEFB4 genomic copy number in SLE and ANCA-associated small vasculitis

Abstract

Evidence shows that defensins are involved in the pathogenesis of SLE and ANCA-associated small vasculitis (AASV). The copy number variation of DEFB4 has been proposed to be susceptible to inflammatory disorders. This study aims to investigate whether the DEFB4 genomic copy number variations associate with the susceptibility to these two autoimmune diseases. A total of 1178 Chinese people were enrolled, including panel 1 comprising 240 SLE patients and 275 matched controls, panel 2 comprising 303 SLE patients and 248 matched controls and panel 3 with 112 AASV patients. The DEFB4 copy number was typed by a paralogue ratio test (PRT), and all the subjects in panel 1 were also typed using the restriction enzyme digest variant ratio (REDVR) for validation. The results from PRT and REDVR were highly concordant (R = 0.911, P = 3.85 × 10(-199)) and allowed copy numbers to be assigned into integer classes with high confidence. Comparison of mean DEFB4 copy number revealed a small increase in cases with SLE both in Panel 1 (P = 0.063) and Panel 2 (P = 0.017). When pooling panels 1 and 2 together, the association was reinforced (P = 0.002) in SLE. Such association was also observed in AASV (P = 0.009). We found that a higher DEFB4 gene copy number was associated with both SLE and AASV.