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Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis
F Takeuchi1, K Nakano, K Matsuta
1Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Insights
The HLA-DRB1*0405 genotype is linked to rheumatoid arthritis (RA) susceptibility in Japanese patients, while HLA-DRB1*0802 shows a negative correlation. This clarifies genetic factors in RA pathogenesis.
Area of Science:
- Immunogenetics
- Rheumatology
- Human Genetics
Background:
- Rheumatoid arthritis (RA) is a complex autoimmune disease with genetic components.
- The human leukocyte antigen (HLA) system plays a crucial role in immune regulation and disease susceptibility.
Purpose of the Study:
- To investigate the association between specific HLA-DR genotypes and the risk of developing rheumatoid arthritis (RA) in a Japanese population.
- To identify specific HLA-DR alleles that may confer susceptibility or protection against RA in Japan.
Main Methods:
- HLA-DR typing and DRB1* genotyping were performed using polymerase chain reaction (PCR) and PCR-single-stranded DNA conformation polymorphism (SSCP).
- Statistical analysis was employed to determine the significance of observed genotype frequencies in RA patients compared to controls.
Main Results:
- A significantly higher prevalence of HLA-DR4 (57.3%) was observed in Japanese RA patients (p < 0.05).
- The DRB1*0405 allele was predominantly increased (46.9%, p < 0.05), and DRB1*0401 also showed an increase.
- Conversely, HLA-DR8, particularly DRB1*0802, was significantly lower (1.0%, p < 0.01) in RA patients.
Conclusions:
- The HLA-DRB1*0405 allele is positively associated with rheumatoid arthritis pathogenesis in Japan.
- The HLA-DRB1*0802 allele demonstrates a negative correlation with RA susceptibility in this population.
- These findings highlight the distinct genetic associations of RA in different ethnic groups, with rare Caucasian alleles showing significant correlations in Japan.
Objective:
To clarify the relationship between the HLA-DR genotype and susceptibility to rheumatoid arthritis (RA) in Japanese patients.
Methods:
HLA-DR typing and DRB1* genotyping were carried out by PCR and PCR-SSCP (single stranded DNA conformation polymorphism), respectively.
Results:
In RA, the prevalence of HLA-DR4 was significantly higher (57.3%, p < 0.05). In particular, DRB1*0405 was predominantly higher (46.9%, p < 0.05) and DRB1*0401 was also increased although not significantly. HLA-DR8, especially DRB1*0802, was significantly lower (1.0%, p < 0.01). RA patients homozygous for DRB1*0405 showed slightly higher values for the erythrocyte sedimentation rate, gamma-globulin, and IgG, as well as positivity for rheumatoid factor and high titers for the Waalar-Rose test, and a decrease in the albumin/globulin ratio, albumin, and hemoglobin in comparison to patients without RA susceptibility genes, although the difference for each of these parameters was not significant.
Conclusion:
DRB1*0405 and DRB1*0802, which are both rare alleles in Caucasians, are positively and negatively correlated, respectively, with the pathogenesis of RA in Japan.