Abnormal immune complex clearance is a feature of systemic lupus erythematosus (SLE). Polymorphisms of the Fc gamma receptor type IIa (Fc gammaRIIa) genes (the receptor binds IgG2 and IgG3) are important disease susceptibility factors in some populations. This study sought to determine the effects of these polymorphisms among Korean patients with SLE.Polymerase chain reaction of genomic DNA and allele-specific oligonucleotide hybridization were used to determine Fc gammaRIIa genotypes in Korean patients with SLE and healthy control subjects. Clinical manifestations were analyzed in each patient and correlated with the genotypes.Among the 73 SLE patients, there was an abnormal distribution of Fc gammaRIIa alleles when compared with 64 controls: 11.0% of the SLE patients were homozygous for Fc gammaRIIa-H131 compared with 34.4% of the controls (odds ratio [OR] 0.20, 95% confidence interval [95% CI] 0.04-0.95, chi2 = 5.7, P = 0.01699). The allelic frequency of Fc gammaRIIa-H131 was significantly lower in the SLE patients than in the controls (49.3% versus 63.3%; P = 0.02019), and it was also significantly lower in lupus patients with nephritis compared with the normal population (OR 0.53, 95% CI 0.29-0.95, chi2 = 5.15, P = 0.02330), but was not significantly lower in lupus patients without nephritis (P = 0.13663 versus controls). Clinically, the level of proteinuria was significantly higher in the lupus nephritis patients who had R/R131 than in those who had H/H131 or R/H131.An abnormal distribution of Fc gammaRIIa polymorphisms was associated with SLE in Korean patients. There was a significant decrease in the Fc gammaRIIa-H/H131 genotype and H131 allelic frequency in SLE patients, particularly in those with nephritis. This suggests that the H131 allele confers some protection from SLE in this population.