Abstract
OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).
METHODS: One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied.
RESULTS: The frequency of HLA-DRB1*04 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in DRB1*04, since it was also found among DRB1*04-negative haplotypes (P < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]).
CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.
Original language | English |
---|---|
Pages (from-to) | 315-22 |
Number of pages | 8 |
Journal | Arthritis and rheumatism |
Volume | 44 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2001 |
Externally published | Yes |
Keywords
- Arthritis, Rheumatoid/epidemiology
- Child
- Family Health
- Female
- Finland/epidemiology
- HLA-DP Antigens/genetics
- HLA-DR Antigens/genetics
- HLA-DRB1 Chains
- Haplotypes
- Humans
- Microsatellite Repeats/genetics