The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increased susceptibility and severity in male patients (the Swedish TIRA project).

ABSTRACT

OBJECTIVES: To evaluate the influence of Fcgamma receptor IIIA (FcgammaRIIIA) 158V/F polymorphism on susceptibility and disease severity in early rheumatoid arthritis (RA). METHODS: In 181 Swedish patients (128 women, 53 men) with RA of recent onset, disease and disability variables such as erythrocyte sedimentation rate, 28-joint disease activity score (DAS28) and health assessment questionnaire (HAQ) scores were monitored regularly during 3 yr. Three hundred and sixty-two controls were recruited from the same geographical area as the patients. FcgammaRIIIA genotyping was performed using denaturing high-performance liquid chromatography. RESULTS: In all RA patients, FcgammaRIIIA-158VV was significantly over-represented compared with controls [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.01-3.5, P<0.05]. After stratifying for sex, the difference remained in the male population (OR 3.2, 95%CI 1.03-11, P<0.05) but disappeared among women (OR 1.4, 95%CI 0.7-3.1, P=0.4). In addition, 158VV patients were more likely to exhibit early joint erosions (OR 6.1, 95%CI 1.4-28, P<0.01). At baseline, patients with different FcgammaRIIIA genotypes did not differ with respect to measures of disease activity or functional ability. Thereafter, in male patients with at least one V allele the mean DAS28 and HAQ scores were higher compared with 158FF. In contrast, female patients with at least one 158V allele displayed lower mean DAS28 and HAQ scores compared with those with 158FF. CONCLUSIONS: In a male population, the FcgammaRIIIA-158VV genotype is associated with an increased risk of developing RA, and the 158V allele with more severe disease in early RA.