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Association of DM genes in systemic sclerosis is secondary to the association with HLA genes
F Takeuchi1, K Takizawa, H Nabeta
1Department of Internal Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Abstract:
The contribution of polymorphism of DMA and DMB alleles to the pathogenesis of Japanese Systemic Sclerosis (SSc) was studied in 55 Japanese SSc patients and 77 normal Japanese subjects using the PCR-RFLP (restriction fragment length polymorphism) method. The allele frequencies of DMB*0101 allele were increased in SSc with diffuse scleroderma (70.0% vs 49.4%, p < 0.05, pc = not significant (NS)) and in SSc with antitopoisomerase I antibody (a-Scl-70), (68.2%, p < 0.05, pc = NS). The phenotype frequencies of DMB*0101 in these subgroups of SSc were increased significantly (95.0%, p = 0.014, pc < 0.05; 95.5%, p = 0.0088, pc < 0.05, respectively). In contrast, DMB*0102 and DMB*0103 alleles tended to decrease in diffuse scleroderma and SSc with a-Scl-70, but the decreases were not significant. Association analysis among DMA, DMB, and DRB1*1502 in Japanese SSc with diffuse scleroderma and SSc with a-Scl-70 indicated that the increase in DMA*0101 was not primary, but reflected an increase in HLA DRB1*1502.
Insights
Polymorphism in DMA and DMB alleles may contribute to Japanese Systemic Sclerosis (SSc) pathogenesis. Specifically, the DMB*0101 allele was more frequent in SSc patients, particularly those with diffuse scleroderma or anti-Scl-70 antibodies.
Area of Science:
- Immunogenetics
- Rheumatology
- Molecular Biology
Background:
- Systemic Sclerosis (SSc) is an autoimmune disease with complex pathogenesis.
- Genetic factors, including Human Leukocyte Antigen (HLA) alleles, are implicated in SSc susceptibility.
- The role of specific DMA and DMB gene polymorphisms in Japanese SSc remains to be fully elucidated.
Purpose of the Study:
- To investigate the association between polymorphisms of DMA and DMB alleles and the pathogenesis of Japanese Systemic Sclerosis (SSc).
- To determine if specific allele frequencies correlate with clinical subtypes of SSc, such as diffuse scleroderma and the presence of anti-topoisomerase I antibody (a-Scl-70).
Main Methods:
- Utilized the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method.
- Analyzed allele and phenotype frequencies of DMA and DMB in 55 Japanese SSc patients and 77 healthy Japanese controls.
- Performed association analysis with HLA DRB1*1502.
Main Results:
- The DMB*0101 allele frequency was significantly increased in SSc patients with diffuse scleroderma (70.0% vs 49.4%) and those with a-Scl-70 antibodies (68.2%).
- Phenotype frequencies of DMB*0101 were significantly higher in these SSc subgroups (95.0% and 95.5%, respectively).
- DMB*0102 and DMB*0103 alleles showed a non-significant trend towards decrease in these SSc subgroups.
- Association analysis suggested that the increase in DMA*0101 was secondary to an increased frequency of HLA DRB1*1502.
Conclusions:
- The DMB*0101 allele is associated with an increased risk and specific clinical manifestations (diffuse scleroderma, a-Scl-70 positivity) in Japanese Systemic Sclerosis.
- The observed association of DMA*0101 may be linked to the co-occurrence with HLA DRB1*1502, suggesting a complex genetic interplay in SSc pathogenesis.
- These findings contribute to understanding the genetic underpinnings of Systemic Sclerosis in the Japanese population.