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Dissecting the Genetic Factors Involved in Systemic Lupus Erythematosus Development

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Researchers at the University of Tsukuba have pinpointed a genetic factor in the human leukocyte antigen gene region that is involved in the pathogenesis of systemic lupus erythematosus by analyzing a Japanese population. The same analysis is difficult to perform in European populations owing to their different genetic backgrounds, and the study reinforces the fact that analysis of multiple populations is useful in such cases.

Tsukuba, Japan—Systemic lupus erythematosus (SLE) is a typical autoimmune rheumatic disease. This multifactorial condition results from a combination of multiple genetic and acquired factors. Human leukocyte antigen (HLA), which is responsible for individual differences in immune response, is one of the major genetic factors associated with SLE development. However, its contribution to the pathogenesis of the disease has not been fully elucidated.

The gene sequence associated with SLE susceptibility occasionally varies among populations. In the Japanese population, the gene sequence type HLA-DRB1*15:01 is associated with SLE susceptibility. In the European population, a very high proportion of individuals with HLA-DRB1*15:01 also have specific variants (individual differences in the DNA sequence) in the intergenic region, which is located in the adjacent XL9 region on the chromosome and regulates the expression of the HLA cluster. Consequently, it has been difficult to determine whether HLA-DRB1*15:01 itself or the variants in the XL9 region is important.

In this study, researchers observed that the combination of HLA-DRB1*15:01 and XL9 variants was not as prominent in the Japanese population compared to the European population. Using epidemiological analysis, they were able to distinguish the effects of HLA-DRB1*15:01 and XL9 variants. Of the two, HLA-DRB1*15:01 was primarily associated with the SLE development in the Japanese population, and the association with the XL9 region was secondary, suggesting that differences in amino acid sequences based on the diversity of the HLA itself are likely to influence SLE development.

Furthermore, the study reaffirmed the usefulness of analyzing multiple populations with different genetic backgrounds for identifying genetic variants that contribute to the development of multifactorial diseases.

This study was partly supported by the collaborative research fund from H.U. Group Research Institute G.K., and by award grants given to NTs from Japan College of Rheumatology and Japan Rheumatism Foundation.

Original Paper

Title of original paper:
Genetic dissection of HLA-DRB1*15:01 and XL9 region variants in Japanese patients with systemic lupus erythematosus: primary role for HLA-DRB1*15:01
RMD Open


Professor TSUCHIYA Naoyuki
Assistant Professor KAWASAKI Aya
Institute of Medicine, University of Tsukuba

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