Figure 2 Interaction effects between heterozygous HLA‑DRB1

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Figure 2 Interaction effects between heterozygous HLA‑DRB1 alleles on anti-citrullinated protein autoantibody-positive rheumatoid arthritis risk Figure 2 | Interaction effects between heterozygous HLA-DRB1 alleles on anti-citrullinated protein autoantibody-positive rheumatoid arthritis risk. Non-log-additive interaction effects between heterozygous HLA-DRB1 alleles generally increase the risk of anti-citrullinated protein autoantibody (ACPA)-positive rheumatoid arthritis (RA). Homozygotes for HLA-DRB1 allele A (red) or B (blue) express homogenous HLA-DR proteins A or B, by which autoantigens are presented in an allele-specific manner. Individuals who have heterozygous HLA-DRB1 alleles might have larger autoantigen repertoires than homozygotes, and the existence of two different alleles might provide additional codominant risk effects because of the likelihood of presenting various kinds of autoantigens. The codominance effect of two alleles is statistically well explained by the interaction term ORA*B. AgA, antigens presented by HLA-DR molecule A; AgB, antigens presented by HLA-DR molecule B. Kim, K. et al. (2016) Update on the genetic architecture of rheumatoid arthritis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.176