Coke LN, Wen H, Comeau M, et al. - This study was performed to ascertain whether the polymorphism encoding the Arg206Cys substitution in DNASE1L3 explains the relationship of the DNASE1L3/PXK gene locus with systemic lupus erythematosus (SLE) and to analyze the impact of the Arg206Cys sequence change on DNASE1L3 protein function. Researchers conducted the conditional analysis for rs35677470 on cases and controls with European ancestry from the SLE Immunochip study, and genotype and haplotype frequencies were compared. The results of this study demonstrate that in the DNASE1L3 locus, the SLE risk relationship is dependent on the missense SNP rs35677470, which confers a reduction in DNASE1L3 protein secretion but does not eliminate its DNase enzyme function.