Multiple Membrane Transporters and Some Immune Regulatory Genes are Major Genetic Factors to Gout

Abstract

Gout is a common form of inflammatory arthritis caused by hyperuricemia and the deposition of Monosodium Urate (MSU) crystals. It is also considered as a complex disorder in which multiple genetic factors have been identified in association with its susceptibility and/or clinical outcomes. Major genes that were associated with gout include URAT1, GLUT9, OAT4, NPT1 (SLC17A1), NPT4 (SLC17A3), NPT5 (SLC17A4), MCT9, ABCG2, ABCC4, KCNQ1, PDZK1, NIPAL1, IL1β, IL-8, IL-12B, IL-23R, TNFA, MCP-1/CCL2, NLRP3, PPARGC1B, TLR4, CD14, CARD8, P2X7R, EGF, A1CF, HNF4G and TRIM46, LRP2, GKRP, ADRB3, ADH1B, ALDH2, COMT, MAOA, PRKG2, WDR1, ALPK1, CARMIL (LRRC16A), RFX3, BCAS3, CNIH-2, FAM35A and MYL2-CUX2. The proteins encoded by these genes mainly function in urate transport, inflammation, innate immunity and metabolism. Understanding the functions of gout-associated genes will provide important insights into future studies to explore the pathogenesis of gout, as well as to develop targeted therapies for gout.

RETRACTED ARTICLE: Clostridium difficile toxin B induces colonic inflammation through the TRIM46/DUSP1/MAPKs and NF-κB signalling pathway

“…Given the role of TcdB in the ubiquitination of DUSP1, the E3-ubiquitin ligases TRIM family proteins that are associated with inflammatory response were increased by TcdB in FHC cells, with the most increased expression of TRIM46. TRIM46 was associated with gout, a common form of inflammatory arthritis caused by hyperuricaemia [31]. TcdB activated NF-jB and MAPKs signalling pathways and induced release of TNF-a and IL-1b were inhibited by TRIM46 silencing, suggesting its important role in TcdB-induced colonic inflammation.…”

“…As expected, treatment of FHC cells with TcdB at concentrations ranging from 100 to 400 significantly induced DUSP1 ubiquitination in a dose-dependent manner (Figure 2(D)). Meanwhile, TRIM family proteins that act as E3-ubiquitin ligases, including TRIM8, TRIM11, TRIM22, TRIM24, TRIM46, TRIM52, TRIM65 and TRIM68, have been found to be associated with inflammatory response [20][21][22][29][30][31][32][33] and are therefore examined in response to TcdB. As shown in Figure 2(E), FHC cells with 200 ng/ml TcdB treatment for 24 h markedly decreased the mRNA expression of TRIM22 by 18.6% and increased the mRNA expression of TRIM8, TRIM11, TRIM24, TRIM46, TRIM52 and TRIM65 by 20.8%, 48.7%, 24.6%, 200.9%, 50.1% and 103.8%, respectively, compared with control.…”

The Genetic Basis of Thyroid Function: Novel Findings and New Approaches

“…The most recent GWAS on FT4 levels identified two independent variants within the SLC17A4 gene (rs9356988 and rs137964359) to be associated with FT4 levels (19). The SLC17A4 gene encodes an organic anion transporter that is particularly expressed in the liver, kidney, and gastrointestinal tract (56,57). Given its association with TH levels, it was postulated that SLC17A4 could encode a TH transporter.…”

Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

“…There are other urate transporters in the proximal tubules that are also responsible for uric acid transport, i.e., NPT1 (solute carrier family 17 member 1, SLC17A1), NPT4 (solute carrier family 17 member 3, SLC17A3), OAT4 (solute carrier family 22 member 11, SLC22A11), OAT10 (solute carrier family 22 member 13, SLC22A13), and MRP4 (ATP binding cassette subfamily C member 4, ABCC4) [2,15]. However, recent evidence suggests that these proteins have less impact on uric acid levels in the blood than GLUT9, URAT1, and ABCG2 [2,16].…”