The role of NLRP3 and CARD8 polymorphisms in the risk of rheumatoid arthritis: A meta‐analysis of genetic association studies

Abstract

ObjectiveTo investigate the potential associations between rheumatoid arthritis (RA) and NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3) rs35829419, rs10754558, s4612666, and caspase recruitment domain family member 8 (CARD8) rs2043211 polymorphisms.MethodsRelevant papers were searched for in MEDLINE, Embase, and Web of Science. Allele contrast, recessive, dominant, and homozygote contrast models were used to investigate the relationship between the NLRP3 rs35829419, rs10754558, and s4612666, and CARD8 rs2043211 polymorphisms and RA. This review was registered with PROSPERO (CRD42023451231).ResultsThe meta‐analysis included 11 comparative studies comprising 3789 patients with RA and 3956 controls. No significant association was found between NLRP3 rs35829419 C allele and RA in Europeans, Arabs, or Latinos. The NLRP3 rs10754558 G allele was not associated with RA in the Asian or Arab populations. However, a single study in Latin America discovered a link between RA and the NLRP3 rs10754558 G allele. The NLRP3 rs4612666 T allele was not associated with RA, according to the meta‐analysis. When ethnicity was stratified, there was no association between the NLRP3 rs4612666 T allele and RA, except for a single study that found an association among Arabs. The CARD8 rs2043211 T allele did not seem to be associated with RA. According to an ethnic stratification study, the CARD8 rs2043211 T allele did not appear to be associated with RA in Europeans, Arabs, or Latinos.ConclusionsThe meta‐analysis indicated that the NLRP3 rs35829419, rs10754558, and s4612666 polymorphisms, as well as the CARD8 rs2043211 polymorphism, were not linked to RA susceptibility.

CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity

“…Several publications also claim a role for CARD8 in rheumatoid arthritis (RA) [ 103 , 105 , 106 , 107 , 108 , 165 ]. However, whether rs2043211 is indeed associated with RA is controversially discussed [ 57 , 110 ]. Similarly, there is evidence that carriers of rs2043211 have an increased risk for developing IBD [ 94 , 115 ].…”

“…-Worse pathogenesis of rheumatoid arthritis with NLRP3 rs35829419 [103] or rs4612666 [104]. -Associated with rheumatoid arthritis [103,[105][106][107][108][109], or no association [57,110,111]. -Protective against SARS-CoV-2 [112].…”