Related Experiment Videos
Association of DMA and DMB with RA in Japanese
F Takeuchi1, H Nabeta, S Kuwata
1Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Objective:
The contribution of polymorphism of DMA and DMB alleles to the pathogenesis of Japanese RA was studied. The association of DM alleles with HLA-DRB1*0405 and *0802, which were positively and negatively susceptible to Japanese RA, respectively, is also discussed.
Methods:
DMA and DMB typing was carried out in 91 Japanese RA patients and in 77 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DRB1*04 and *08 genotyping were carried out by the PCR-SSCP (single-stranded DNA conformation polymorphism) method.
Results:
Allele frequencies of DMB*0101 and DMB*0102 were slightly higher (52.2% and 27.0%) and the allele frequency of DMB*0103 was slightly lower (25.8%) in RA, but these differences were not significant. The increase of DMB*0102 was due to a negative association with HLA-DRB1*0802 [p < 0.05, pc = not significant (NS)]. The decrease of DMB*0103 was due to a positive association with DRB1*0802 (p < 0.005, pc < 0.05). The increase of DMB*0101 was possibly due to a weak association with HLA-DRB1*0405, (p = NS). Positivity of rheumatoid factor did not affect the prevalence of DMA and DMB alleles.
Conclusion:
Association analysis among DMA, DMB and DRB1 (*0405 and *0802) indicate that slight increases or decreases in DMB*0101, DMB*0102 and DMB*0103 are not primary indicators but reflect an increase in HLA-DRB1* 0405 and a decrease in HLA-DRB1*0802 in Japanese RA.
Insights
Polymorphisms in DMA and DMB alleles are not primary indicators of Japanese rheumatoid arthritis (RA) pathogenesis. Their frequencies reflect associations with HLA-DRB1*0405 and HLA-DRB1*0802 susceptibility in RA patients.
Area of Science:
- Immunogenetics
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a complex autoimmune disease with a significant genetic component.
- Human Leukocyte Antigen (HLA) genes, particularly HLA-DRB1, are strongly associated with RA susceptibility.
- The role of other genetic polymorphisms, such as those in DMA and DMB genes, in RA pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the contribution of DMA and DMB allele polymorphisms to the pathogenesis of Japanese RA.
- To examine the association of DM alleles with specific HLA-DRB1 alleles (HLA-DRB1*0405 and HLA-DRB1*0802) known to influence RA susceptibility in the Japanese population.
Main Methods:
- Genotyping of DMA and DMB alleles was performed using the PCR-RFLP method in 91 Japanese RA patients and 77 healthy controls.
- HLA-DRB1*04 and *08 genotyping was conducted using the PCR-SSCP method.
Main Results:
- No significant differences in allele frequencies of DMB*0101, DMB*0102, and DMB*0103 were observed between RA patients and controls.
- DMB*0102 showed a negative association with HLA-DRB1*0802, while DMB*0103 demonstrated a positive association with HLA-DRB1*0802.
- DMB*0101 exhibited a potential weak association with HLA-DRB1*0405, though not statistically significant.
Conclusions:
- The observed minor fluctuations in DMA and DMB allele frequencies are not primary indicators of RA pathogenesis.
- These variations in DMA and DMB alleles appear to be secondary to the established associations with HLA-DRB1*0405 and HLA-DRB1*0802 in Japanese RA.