The FcγRIIIA-158F allele is a risk factor for systemic lupus erythematosus

Objective. To study whether the FcγRIIIA-158V/F polymorphism, which affects IgG binding affinity, is a risk factor for systemic lupus erythematosus (SLE). Methods. We genotyped a group of 70 Caucasian SLE patients for all known FcγR polymorphisms. Of this group, 45 patients (64%) had nephritis. In 35 patients, this diagnosis was confirmed by renal biopsy. Results. In the total group of 70 SLE patients, the frequency of the FcγRIIIA-158F allele was 0.74, versus 0.57 in healthy controls (P = 0.003). The genotype distribution of the FcγRIIIA-158V/F polymorphism was also significantly different from that of the control population (P = 0.004). The distribution of the other FcγR polymorphisms - FcγRIIA-131R/H, FcγRIIIB- NA(1,2), and FcγRIIIA-48L/R/H - was similar in SLE patients and controls. Conclusion. In our group of SLE patients, only the distribution of the alleles of the FcγRIIIA-158V/F polymorphism was significantly different from that in the control group. This might indicate that macrophage expression of the FcγRIIIA-158F isoform is involved in the disturbed clearance of immune complexes in patients with SLE.