NLRP3 genetic variants and their impact on psoriasis susceptibility, severity, and risk of psoriatic arthritis

Psoriasis (PsO) is a chronic, immune-mediated inflammatory disease with systemic manifestations. Its etiology involves an interaction between genetic, immunologic, and environmental factors. The NLRP3 inflammasome plays a key role in innate immune responses and has been implicated in PsO pathogenesis. However, data regarding NLRP3 gene polymorphisms and their relationship with PsO, particularly in the Brazilian population, remain limited. The aim was to investigate the association between the NLRP3 rs10157379 and rs10754558 gene variants with susceptibility and severity of PsO, as well as the risk of developing psoriatic arthritis (PsA). A case-control study was conducted with 154 individuals with PsO and 154 healthy controls. Clinical and demographic data were collected, and genotyping of the NLRP3 rs10157379 T > C and rs10754558 G > C variants was performed using real-time polymerase chain reaction. No significant association was observed between either variant and PsO susceptibility or severity. However, the rs10754558 CG genotype was associated with a reduced likelihood of PsA [odds ratio (OR): 0.32; 95 % confidence interval (CI): 0.10-0.95, p = 0.041], while the GG genotype conferred a higher likelihood (OR: 3.26; 95 % CI:1.03-10.32, p = 0.044). No associations were identified for the rs10157379 variant. In conclusion, the NLRP3 rs10157379 and rs10754558 variants were not associated with PsO susceptibility or severity. However, the rs10754558 variant may influence the chance of joint involvement in individuals with PsO. These findings underscore the potential role of NLRP3 variants in PsA development and highlight the importance of genetic background in PsO pathophysiology.