HLA-DRB1-ASTERISK-0401 0404 GENOTYPE AND RHEUMATOID-ARTHRITIS - INCREASED ASSOCIATION IN MEN, YOUNG AGE AT ONSET, AND DISEASE SEVERITY/

Objective. To confirm the reported strong association between the HLA- DRB10401/0404 genotype and susceptibility to rheumatoid arthritis (RA ), and to investigate the influence of sex, age at disease onset, and variables of disease severity on the strength of this association. Met hods. A case control design was adopted comparing the frequency of spe cific HLA-DRB1 genotypes between 201 Caucasian patients with RA and 13 9 controls. HLA typing was performed using a polymerase chain reaction based oligonucleotide approach with BLA-DR4 subtyping using an amplif ication refractory mutation system RFLP technique. Results. The risk o f RA in those carrying a single shared epitope (SE) allele was 4 times , and in those carrying 2 SE alleles, 8 times that in the SE negative individuals. This increase was highest in individuals carrying 2 diffe rent SE alleles, with the risk in 0401/*0404 cases being 26 times hig her. This genotype was associated with a 90-fold increased risk in men and this was more than doubled when age at disease onset was below 30 . In all patients with RA, this genotype was associated with a substan tially increased risk of being rheumatoid factor positive and having s ubcutaneous nodules and/or radiological erosion. Conclusion. Possessio n of the BLA-DRB10401/*0404 genotype carries a substantially high ris k for RA development specifically in its more severe forms. The risks are particularly increased in young men.