Table 3.
Examples of antagonistic pleiotropy for genes that increase risk or severity of chronic inflammatory diseases
| Genes | Chronic inflammatory disease | Pleiotropic meaning outside of chronic inflammatory diseases (with selection advantage) | Refs. |
|---|---|---|---|
| HLA DR4 (DRB1*04) | Rheumatoid arthritis and other autoimmune diseases | Decrease of risk of dengue hemorrhagic fever (defense against infectious agents) | [21] |
| HLA B27 | Ankylosing spondylitis and other axial forms of spondyloarthritis | Decrease of viral infection (defense against infectious agents) | [57, 58] |
| PTPN22 1858 C>T* | Many autoimmune diseases | Higher body mass index, higher waist-to-hip ratio in women (storage of energy-rich fuels) | [59] |
| CTLA4 49 A>G | Many autoimmune diseases | Better defense against hepatitis B virus and Helicobacter pylori (defense against infectious agents) | [60, 61] |
| NOD2/CARD15 | Crohn’s disease | Hypertension (activation of the sympathetic nervous system) | [62] |
*PTPN22 1858 C>T is associated with many autoimmune diseases but is also linked to a higher risk of infection. This seems to contradict the theory of antagonistic pleiotropy. Until today, nobody has focused on a possible selection advantage in the context of reproduction. It might well be that this mutation is related to a decreased T cell - dependent rejection of the semiallogenic fetus. This would support reproduction. The PTPN22 1858 C>T mutation is linked to increased risk of endometriosis which already demonstrates a role in the context of reproduction [63]