It is well-known that NLRP3 is closely related to the onset of primary gout (PG). However, the relation between NLRP3 gene transcript variants and the occurrence of PG remains unclear. This study was undertaken to evaluate whether NLRP3 gene transcript variants are involved in the occurrence of PG. A total of 44 acute phase PG (APPG), 52 non-acute phase PG (NAPPG) male patients, and 30 male health control (HC) were involved in this study. We measured NLRP3 and its transcript variants 2, 3, 4, 5, and 1 + 6 expressions in the PBMCs, together with the level of IL-1β in the serum. Further, PBMCs of HC were stimulated with MSU crystals. The levels of NLRP3, NLRP3 gene transcript variants 2, 3, 4 mRNA, and protein expressions were significantly lower in the APPG and NAPPG groups than in the HC group (P < 0.05, respectively), and IL-1β expression was significantly higher in the APPG group than in the HC and NAPPG groups (P < 0.05, respectively). Levels of IL-1β and NLRP3-4 mRNA expressions were negatively correlated with APPG group (r = - 0.2828, P = 0.0252). After stimulating PBMCs of HC with MSU crystals, levels of NLRP3, NLRP3-4 mRNA, and NLRP3 protein expressions were reduced significantly (P < 0.05, respectively), and the level of IL-1β in MSU group was increased significantly (P < 0.05). Here, we show that NLRP3-4 transcript variant may be closely related to the occurrence of PG. Thus, NLRP3-4 gene transcript variant may provide a novel target for the diagnosis and therapy of PG.
Keywords: Gout; Inflammasome; Monosodium urate crystals; NLRP3; Transcript variant.