The aim of this study was to determine the distribution of the FcgammaRlla and FcgammaRIIIa 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 FcgammaRlla 131 R/H and FcgammaRIIIa 176 F/V was performed by PCR of genomic
DNA using allele-specific primers and the FcgammaRIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three
FcgammaRIIa genotypes between the SLE and the controls (P=0.002 for R/R131 vs R/H131 and H/H131, OR 2.5 (95% Cl 1.4-4.5), but not in FcgammaRIIIa genotypes.
FcgammaRIIa-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% Cl 1.03-1.9)), but proliferative
nephritis (WHO class III and IV) was less common in patients with FcgammaRlla-R/R131 and in
FcgammaRIIa-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
FcgammaRIIa/FcgammaRIIIa 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
FcgammaRIIa-R/R131 or R131-allele than male controls, but
FcgammaRIIa or FcgammaRIIIa genotypes had no association with renal involvement in male SLE patients.
FcgammaRIIa-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-Ro antibody (+) than male SLE, and had earlier onset of first symptoms. There was no skewing in
FcgammaRIIa or FcgammaRIIIa genotypes between female SLE and female controls, but
FcgammaRIIa-R131 allele showed skewing between female SLE with
nephritis and female SLE without
nephritis. The age at onset of
thrombocytopenia was earlier in
FcgammaRIIa R/R131 among three
FcgammaRIIa genotypes, and
serositis in FcgammaRIIIa-F/F176 among three FcgammaRIIIa genotypes.
FcgammaRIIa-R131 homozygote was a major predisposing factor to the development of SLE and
FcgammaRIIa-RI31 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
FcgammaRIIa and FcgammaRIIIa showed somewhat different clinical associations between the genders.