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  • Review Article
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Mechanisms of Disease: genetics of rheumatoid arthritis—ethnic differences in disease-associated genes

Abstract

Large studies on the genetics of common rheumatic diseases, such as rheumatoid arthritis and systemic lupus erythematosus, have identified multiple polymorphisms related to disease susceptibility, including peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase N22 (PTPN22). Some of the identified genes are associated with multiple autoimmune disorders, and some seem to have unique associations with particular disease entities. Although the molecules encoded by these genes have a primary role in the molecular pathways of autoimmunity, genetic variations and contribution to disease susceptibility seem to vary between ethnic groups. In this Review, we report the findings on genes associated with rheumatoid arthritis and focus on the differences in the frequency of polymorphisms between various ethnic groups.

Key Points

  • Polymorphisms associated with susceptibility to developing rheumatoid arthritis (RA) have been identified in multiple genes, including PADI4 and PTPN22

  • Results of genetic studies indicate that functional pathways that involve genes with polymorphisms associated with RA risk have a primary role in the pathogenesis of the disease

  • Some RA-susceptibility polymorphisms are disease-specific and some are seen in multiple autoimmune disorders

  • Some polymorphisms are unique to a specific ethnic group and some are common across multiple ethnic groups

  • Despite not all disease susceptibility polymorphisms being present across all ethnic groups, their existence indicates roles in disease-related pathological processes

  • Investigations of the ethnic heterogeneity of genetic factors will provide information about disease heterogeneity and facilitate individualized medicine

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Figure 1: Co-plots of allele frequency of common SNPs in the HapMap project (a subset of SNPs in the genome) to show heterogeneity among ethnic groups.
Figure 2: Contributing factors in the development of RA.

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Acknowledgements

The authors thank A Suzuki, Y Kochi, and M Mori, Laboratory for Rheumatic Diseases, SNP Research Center, RIKEN, Japan, for discussion of the topic, and all contributors to the HapMap Project for their public data.

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Correspondence to Kazuhiko Yamamoto.

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The authors declare no competing financial interests.

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Yamada, R., Yamamoto, K. Mechanisms of Disease: genetics of rheumatoid arthritis—ethnic differences in disease-associated genes. Nat Rev Rheumatol 3, 644–650 (2007). https://doi.org/10.1038/ncprheum0592

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