Table 5.
Pharmacogenetics of Biological Agents in Rheumatoid Arthritis (RA)
| Gene Symbol | Polymorphism Position | Alleles | Possible Effect of Polymorphism | Pharmacogenetics | References |
|---|---|---|---|---|---|
| TNFα | +489 | G A |
More severe erosive disease | No effect on response to Etanercept | [95] |
| -238 | G A |
More severe articular erosions Less severe articular erosions |
No effect on response to Etanercept | [95] | |
| -308 | G A |
Normal production of TNFα Up-regulation of TNFα production |
Increased response to Infliximab | [100, 101] | |
| -857 | C T |
Susceptibility to RA / High TNFα production | Increased response to Etanercept | [97] | |
| TNFa11;b4 | haplotype | Influence production of TNFα / Found with D6S273_4/BAT2_2 | Increased response to Infliximab | [11] | |
| TNFRSF1B | codon 196 | T G |
More effective in increasing IL-6 production | Increased response to anti-TNF therapy | [98] |
| IL-1 | IL-1α +4845 (exon 5) |
G T |
Altered production of IL-1α / Increased susceptibility to RA | Increased response to Anakinra | [104] |
| IL-10 | -1082 | G A |
Up-regulation of IL-10 production in lymphocytes Lower expression levels of IL-10 / Associated with RA in women |
Increased response to Etanercept in combination with TNFα -308G/G | [12] |
| -819 | T C |
Lower expression levels of IL-10 / Autoimmune manifestations | Patients with low inflammatory haplotype | ||
| -592 | A C |
Lower expression levels of IL-10 / Autoimmune manifestations | are better Etanercept responders | ||
| HLA | Specific shared epitope alleles (HLA-DR) | May increase susceptibility to and severity of RA | Specific HLA-DRB1 alleles and haplotypes markers of better response to Etanercept | [95] | |
| HLA microsatelites BAT2,D6S273,D6S2223 | Haplotype may carry "response gene" | D6S273_4/BAT2_2 haplotype correlates with increased response to Infliximab | [11] | ||
TNF-α = tumor necrosis factor-α; TNFRSF1B = TNFreceptor; IL-1 = interleukin-1; IL-10 = interleukin-10.