Fc gamma RIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients

The aim of this study was to determine the distribution of the Fc gamma RIIa and Fc gamma RIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients. Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for Fc gamma RIIa 131 R/H and Fc gamma RIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the Fc gamma RIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three Fc gamma RIIa genotypes between the SLE and the controls (P = 0.002 for R/R131 vs R/H131 and H/H131, OR 2.5 (95% CI 1.4-4.5), but not in Fc gamma RIIIa genotypes. Fc gamma RIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P = 0.034 for R131 vs H131, OR 1.4 (95% CI 1.03-1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with Fc gamma RIIa-R/R131 and in Fc gamma RIIa-R allele. In 300 SLE patients, high binding allele combination H131/V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131/F176 allele combination among four Fc gamma RIIa/Fc gamma RIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of Fc gamma RIIa-R/R131 or R131-allele than male controls, but Fc gamma RIIa or Fc gamma RIIIa genotypes had no association with renal involvement in male SLE patients. Fc gamma RIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anticardiolipin antibody (+) and anti-Re antibody (+) than male SLE, and had earlier onset of first symptoms. There was no skewing in Fc gamma RIIa or Fc gamma RIIIa genotypes between female SLE and female controls, but Fc gamma RIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in Fc gamma RIIa-R/R131 among three Fc gamma RIIa genotypes, and serositis in Fc gamma RIIIa-F/F176 among three Fc gamma RIIIa genotypes. Fc gamma RIIa-R131 homozygote was a major predisposing factor to the development of SLE and Fc gamma RIIa-R131 homozygote and R131 allele were a predisposing factor, and H131/V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and Fc gamma RIIa and Fc gamma RIIIa showed somewhat different clinical associations between the genders.