@misc{10481/64327,
year = {2020},
month = {3},
url = {http://hdl.handle.net/10481/64327},
abstract = {This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA− = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.},
organization = {GENYO},
organization = {FIBAO foundation (Granada, Spain)},
organization = {Novo Nordisk Foundation
	
NNF15OC0016932},
organization = {Knud og Edith Eriksens Mindefond 	
A2037
A3570},
organization = {Gigtforeningen 	
A2037
A3570},
organization = {Spinoza grant from the Netherlands Organization for Scientific Research},
publisher = {Springer Nature},
keywords = {Diagnostic markers},
keywords = {Prognostic markers},
keywords = {Rheumatoid arthritis},
title = {NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium},
doi = {10.1038/s41598-020-61331-5},
author = {Sánchez Maldonado, José and Martínez Bueno, Manuel and Jurado Chacón, Manuel and López Nevot, Miguel Ángel and Cáliz Cáliz, Antonio Rafael and Sáinz Pérez, Juan},
}