Table 1.
Genetic variants in the DNA/RNA-IFN signaling pathway that contributes to the progression of LN.
| Locus | Genetic variants | References |
|---|---|---|
| TLR | TLR9 (rs352140) | (91) |
| TLR7 (rs385389) | (92) | |
| TLR5 (rs5744168) | (91) | |
| TLR3 (rs3775291, rs3775294) | (93) | |
| RIG-I/MDA5 | VISA (rs17857295, rs2326369) | (94) |
| IRF | IRF3 (rs7251) | (95) |
| ITGAM (rs1143678, rs1143679, rs1143683) | (96) | |
| NF-κB | TNIP1 (rs7708392, rs4958881) | (97, 98) |
| MiR-146a (rs2431697) | (99) | |
| STAT | STAT4 (rs7582694) | (100) |
TLR9 (rs352140) (91)、TLR7 (rs385389) (92)、TLR5 (rs5744168) (91)、TLR3 (rs3775291 and rs3775294) (93)、IRF3 (rs7251) (95)、STAT4 (rs7582694) (100) are significantly associated with LN. Moreover, TNIP1 (rs7708392 and rs4958881) are associated with the risk of LN and may be involved in the disease development through abnormal regulation of NF-κB and mitogen-activated protein kinase activity (97, 98). MiR-146a (rs2431697T allele) may also increase the occurrence of LN by regulating IFN-I and NF-κB pathways (99). ITGAM variants reduce nuclear FoxO3 protein levels, thereby eliminating inhibition of IRF7 and enhancing the production of IFN-I (96, 101), which give a high risk of SLE and LN (102). Virus-induced signaling adapter (VISA) is an important adaptor protein that connects RIG-I and MDA5 with downstream signaling events. VISA rs17857295 and rs2326369 are associated with the occurrence of LN (94). MDA5, melanoma differentiation-associated protein 5; RIG-I, retinoic acid-inducible gene I; TLR, Toll-like receptor; VISA, virus-induced signaling adapter.