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Association of complement alleles C4AQ0 and C4B5 with rheumatoid arthritis in Koreans
1Department of Clinical Pathology, Seoul National University College of Medicine, Korea.
Insights
Complement C4 allotypes C4AQ0 and C4B5 are linked to rheumatoid arthritis susceptibility in Koreans. C4B5 is associated with HLA-DR4, while C4AQ0 appears to be an independent risk factor.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease.
- The complement system, particularly C4 allotypes, plays a role in immune regulation.
- Genetic factors influencing RA susceptibility are actively researched.
Purpose of the Study:
- To determine the association between complement C4 allotypes and rheumatoid arthritis in the Korean population.
- To investigate the relationship between C4 allotypes, HLA antigens, and rheumatoid factor status in Korean RA patients.
Main Methods:
- Typing of C4 allotypes and HLA-A, B, C, DR, and DQ antigens.
- Comparison of allele frequencies between 65 RA patients and 255 healthy Korean controls.
- Analysis of associations within RA patient subgroups based on rheumatoid factor (RF) status.
Main Results:
- Significantly higher frequencies of C4AQ0 and C4B5 were observed in Korean RA patients compared to controls.
- C4AQ0 frequency was elevated in both RF-positive and RF-negative RA subgroups.
- C4B5 and HLA-DR4 frequencies were increased in the RF-positive subgroup, with a strong association between C4B5 and HLA-DR4.
Conclusions:
- C4AQ0 and C4B5 are associated with rheumatoid arthritis susceptibility in Koreans.
- C4B5 shows a strong association with HLA-DR4.
- C4AQ0 is identified as a potential DR4-independent risk factor for RA in this population.
Objective:
To investigate the association of complement C4 allotypes with rheumatoid arthritis in Koreans.
Methods:
65 rheumatoid arthritis patients and 255 controls were typed for C4 allotypes and HLA-A, B, C, DR, and DQ antigens.
Results:
The frequencies of C4AQ0 (32.3% v 14.9%, P < 0.005) and C4B5 (29.2% v 12.2%, P < 0.005) were significantly increased in rheumatoid arthritis patients compared with healthy control subjects. Among rheumatoid patients, the frequency of C4AQ0 was significantly increased in both the rheumatoid factor (RF) positive (27.3%) and the RF negative (66.7%) subgroups. The frequencies of C4B5 and HLA-DR4 were significantly increased only in RF positive subgroup. C4B5 was strongly associated with HLA-DR4, whereas C4AQ0 did not show association with DR4.
Conclusions:
In Koreans, C4AQ0 and C4B5 are associated with susceptibility to rheumatoid arthritis, as in the Japanese. C4B5 is strongly associated with HLA-DR4. C4AQ0 is considered to be a DR4 independent risk factor, and a disease susceptibility allele in linkage disequilibrium with C4AQ0 is suggested in Korean patients with rheumatoid arthritis.