Association between functional NLRP3 polymorphisms and susceptibility to autoimmune and inflammatory diseases: a meta-analysis

Objective This study determined whether NLRP3 polymorphisms rs35829419 C/A and rs10754558 C/G were associated with autoimmune and inflammatory diseases. Methods An association between the NLRP3 rs35829419 C/A and rs10754558 C/G polymorphisms and autoimmune and inflammatory diseases was determined by performing a meta-analysis by using (1) allele contrast, (2) recessive, (3) dominant, and (4) co-dominant models. Results Thirty comparative studies involving 8069 patients and 8824 controls were included in the meta-analysis. No association was observed between autoimmune and inflammatory diseases and NLRP3 rs35829419 C allele (OR=1.020, 95% CI=0.804-1.295, p=0.869). Stratification by ethnicity showed no association between the NLRP3 rs35829419 C allele and autoimmune and inflammatory diseases in European, Latin American, and Polynesian populations. Stratification by disease type showed no association between the NLRP3 rs35829419 C allele and gout, SLE, RA, celiac disease, and Crohn's disease. Moreover, no association was observed between autoimmune and inflammatory diseases and the NLRP3 rs10754558 C allele (OR=1.057, 95% CI=0.950-1.177, p=0.310). However, stratification by ethnicity showed an association between the NLRP3 rs10754558 C allele and autoimmune and inflammatory diseases in the Latin American (OR=1.399, 95% CI=1.201-1.630, p=1.6x10(-6)) but not in European and Asian populations. Further, stratification by disease type showed a significant association of the NLRP3 rs10754558 C allele with SLE (OR=1.465 95% CI=1.144-1.875, p=0.002) but not with gout and celiac disease. The same pattern was observed for the NLRP3 rs10754558 C allele in the recessive model. Conclusions Our results indicated that the NLRP3 rs10754558 C/G polymorphism was associated with susceptibility to SLE and with autoimmune and inflammatory diseases in Latin American individuals.