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Chronic inflammation is the cause of chronic kidney disease (CKD). The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a vital role in the inflammation process and is associated with the regulatory effects of  NLRP3  gene polymorphisms. This study evaluated the association between  NLRP3  gene polymorphisms and CKD, and further explored whether the association of environmental metals with CKD varied by the  NLRP3  genotypes. A total of 218 CKD patients and 427 age- and sex-matched healthy controls were recruited in this clinic-based case–control study. Patients were identified as having CKD if their estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m 2  and stage 3–5 for at least 3 months. We examined the genotypes of fifteen common ssingle-nucleotide polymorphisms in  NLRP3  genes. Concentrations of total urinary arsenic were examined by summing of urinary inorganic arsenic species. Concentrations of selenium, cadmium, and lead were measured from blood samples. Associations between  NLRP3  polymorphisms, environmental metals exposure, and CKD were evaluated using multivariable logistic regression while controlling for confounders. We observed that the odds of carrying  NLRP3  rs4925650 GA/AA genotypes,  NLRP3  rs1539019 CA/AA genotypes, and  NLRP3  rs10157379 CT/TT genotypes were significantly higher among CKD cases compared to controls, with the adjusted odds ratio (95% confidence interval) were 1.54 (1.01–2.36), 1.56 (1.04–2.33), and 1.59 (1.05–2.38), respectively. The significant multiplicative interactions were identified between high levels of blood lead and  NLRP3  rs4925650 GA/AA genotypes; high levels of blood cadmium or low levels of plasma selenium and the  NLRP3  haplotype (rs4925648, rs4925650, rs12048215, and rs10754555) C-A-A-C multiplicatively interacted to increase the risk of CKD. Our results imply that  NLRP3  polymorphisms may play an important role in the development of environmental metals exposure related CKD.

Combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and environmental metals exposure on chronic kidney disease