Assessment of genetic polymorphisms within nuclear factor-κB signaling pathway genes in rheumatoid arthritis: Evidence for replication and genetic interaction

• Published in: International immunopharmacology 2021-11, Vol.100, p.108089-108089, Article 108089
• Main Authors: Zeng, Zhen, Sun, Qing-Qing, Zhang, Wei, Wen, Qin-Wen, Wang, Ting-Hui, Qin, Wen, Xiao, Dong-Mei, Zhang, Zhen, Huang, Hua, Mo, Yi-Jun, Wu, Xiu-Di, Cen, Han
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anti-Citrullinated Protein Antibodies - blood; Arthritis; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Association analysis; Biomarkers - blood; Case-Control Studies; Citrulline; Epistasis, Genetic; Female; Gene polymorphism; Genes; Genetic analysis; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Interaction; Male; Middle Aged; NF-kappa B - genetics; NF-κB; NF-κB protein; Nucleotides; Pathogenesis; Pathway; Peptides, Cyclic - immunology; Phenotype; Polymorphism; Polymorphism, Single Nucleotide; Rheumatoid arthritis; Rheumatoid factor; Rheumatoid Factor - blood; Risk Assessment; Risk Factors; Signal transduction; Signal Transduction - genetics; Signaling; Single-nucleotide polymorphism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108089

•NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, CCP-positive RA and RF-positive RA.•TNFAIP3 rs2230926 was significantly associated with CCP-positive RA.•Significant additive interaction between NFKB1 rs28362491 and IKBKE rs12142086, NFKBIE rs2233434 and BLK rs13277113, NFKBIL rs2071592 and TNIP1 rs10036748, UBE2L3 rs5754217 and TNFSF4 rs2205960 was involved in the development of RA.•Significant multiplicative interaction between BLK rs13277113 and UBE2L3 rs5754217, BLK rs13277113 and TNFSF4 rs2205960 was implicatived in the development of RA. This study was performed to replicate the associations of genetic polymorphisms within nuclear factor-κB (NF-κB) signaling pathway genes with rheumatoid arthritis (RA), and to further examine genetic interactions in a Chinese population. A total of eleven single-nucleotide polymorphisms (SNPs) were genotyped in 594 RA patients and 604 healthy controls. Genetic association analysis revealed that NFKBIE rs2233434, TNIP1 rs10036748 and BLK rs13277113 were significantly associated with RA, cyclic citrullinated peptide (CCP)-positive RA and rheumatoid factor (RF)-positive RA, and TNFAIP3 rs2230926 was significantly associated with CCP-positive RA. Significant additive interaction was observed between NFKB1 rs28362491 and IKBKE rs12142086 (RERI = 0.76, 95% CI 0.13–1.38; AP = 0.57, 95% CI 0.11–1.03), NFKBIE rs2233434 and BLK rs13277113 (RERI = 1.41, 95% CI 0.88–1.94; AP = 0.85, 95% CI 0.50–1.20), NFKBIL rs2071592 and TNIP1 rs10036748 (RERI = 0.59, 95% CI 0.17–1.02; AP = 0.46, 95% CI 0.05–0.87), UBE2L3 rs5754217 and TNFSF4 rs2205960 (RERI = 0.50, 95% CI 0.16–0.84; AP = 0.57, 95% CI 0.09–1.05). Significant multiplicative interaction was detected between BLK rs13277113 and UBE2L3 rs5754217 (p = 0.02), BLK rs13277113 and TNFSF4 rs2205960 (p = 0.03). Our results lent further support to the role of NF-κB signaling pathway in the pathogenesis of RA from a genetic perspective.