NFKB1 promoter –94 insertion/deletion ATTG polymorphism (rs28362491) is associated with severity and disease progression of rheumatoid arthritis through interleukin-6 levels modulation in Egyptian patients

Elkhawaga, Samy Y.; Gomaa, Maher H.; Elsayed, Mohsen M.; Ebeed, Ahmed A.

doi:10.1007/s10067-021-05584-z

Cited by 10 publications

(9 citation statements)

References 43 publications

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“…Upon comparing the HAQ-DI values in RA patients grouped according to their rs28362491 genotype, those that carried the Del/Del genotype showed the highest levels, compared to those with the Ins/Del and Ins/Ins genotypes (P = .0028 and .0245, respectively). In concordance with our results, Elkhawaga et al [20] reported that this polymorphism was associated with disease severity and progression in RA patients in Egypt. However, no association of this polymorphism with DAS28 or HAQ was determined in a Brazilian population.…”

Section: Discussionsupporting

confidence: 94%

“…In this study of a Mexican population, we did not find an association of rs28362491 with RA. These results agree with those of Bogunia-Kubik et al, [ 18 ] Gębura et al, [ 26 ] and Gomes da Silva et al, [ 27 ] who also failed to determine an association of rs28362491 with RA in Polish and Brazilian populations, respectively, though Elkhawaga et al [ 20 ] reported that the Del/Del genotype was associated as a risk factor for RA in an Egyptian population. This polymorphism, in particular the Ins allele, has also been associated with other inflammatory diseases, such as Behçet disease [ 28 ] and psoriasis, [ 29 ] while the Ins/Ins genotype has been associated with a higher risk of developing colorectal cancer.…”

Section: Discussionsupporting

confidence: 90%

“…[12] The uncontrolled activation of the NFkB signaling pathway has been involved in promotion of the inflammatory response in different autoimmune disease. [14][15][16][17] The association of the rs28362491 in the NFkB gene with RA has been reported by different groups with contradictory results, [18][19][20] in where the minor allele appears to be dependent of the studied population, and the association of this polymorphism on the clinical features, such as DAS28 and HAQ-DI, have showed also different results.…”

Section: Introductionmentioning

confidence: 99%

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The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis

et al. 2021

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by an inflammatory process that affects mainly synovial tissue in joints, and by the production of cyclic citrullinated peptides (anti-CCP) antibodies. In the inflammatory process the regulation of the nuclear factor kappa B (NFkB) transcription factor activation is a key point in the production of inflammatory cytokines. On the other hand, polymorphisms in several genes could contribute to the promotion of the inflammatory process observed in RA, and the association of the rs28362491 polymorphism in the NFkB gene with RA has been studied in different population. Therefore, it could be one of the interest targets to analyze their association with RA in a Mexican population. This is a case-control study to determine the influence of rs28362491 in the NFkB gene on RA and on clinical features of this disease, such as anti-CCP antibody levels, Disease Activity Score, and Health Assessment Questionnaire-Disability Index. The genotype of rs28362491 in the NFkB gene was determined in 140 RA patients and 135 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method with the enzyme PflMI . The following clinical variables were also determined: anti-CCP levels, Disease Activity Score, and Spanish version of the Health Assessment Questionnaire Disability-Index. Although no association of the polymorphism as a risk/protection factor with RA was found, the RA patients who carried the Ins/Ins genotype showed higher anti-CCP levels, while those with the Del/Del genotype showed higher Spanish version of the Health Assessment Questionnaire-Disability Index levels, compared to the other genotypes. The NFkB -94 Ins/Del ATTG (rs28362491) polymorphism is, therefore, associated with higher levels of anti-CCP antibodies, though no significant association as a risk or protection factor in RA cases was identified.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis

et al. 2021

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“…As reported in previous studies, the susceptible genes of RA could be associated with the severity of the disease [24][25][26]. Elkhawaga et al [24] reported that rs28362491 of NFKB1 contributed to both susceptibility and severity of RA. Zhao et al [25] reported that rs1801278 of IRS-1 was associated with increased risk and disease activity of RA.…”

Section: Discussionmentioning

confidence: 71%

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

Xia¹,

Pan

et al. 2022

J Orthop Surg Res

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Objectives A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. Methods The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. Result For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. Conclusions SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

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“…Additionally, its levels correspond with indicators of activity such as ESR levels, the length of morning stiffness, the number of joints that are sensitive and swollen, the DAS-28, and PDUS. Elkhawaga et al (14) found a connection between the NF-B1 polymorphism and the development of RA. Wang et al (15) believed that IKK was an activity indicator for RA back in 2005.…”

Section: Table (3): Correlation Of Nf-κb1 and Ikkε Gene Expression Le...mentioning

confidence: 99%

Association of NF-κB1/IKKε Gene Expression with Disease Activity Indices in Patients with Early Rheumatoid Arthritis

Rageh¹,

Fawzy²,

Elateek

et al. 2023

The Egyptian Journal of Hospital Medicine

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Background: Pain, swelling, soreness from touching, stiffness in the joints, particularly in the morning, and symmetrical polyarthritis are all symptoms of rheumatoid arthritis (RA), a prevalent form of autoimmune inflammatory arthritis. Objective: This work was aimed to investigate whether there is a correlation between the expression of the nuclear factor kappa beta1/IKK epsilon (NF-κB1/IKKε) gene and disease activity indices in individuals who have early rheumatoid arthritis. Patients and Methods: This study involved 50 patients with newly diagnosed RA and 30 subjects serving as controls. Patients were subjected to detailed medical history, clinical examination, and underwent evaluation of illness severity using disease severity scores (DAS-28). Laboratory investigations, and real time PCR was done for NF-B1/IKK. Examination using power Doppler ultrasonography (PDUS) was carried out on 22 of the joints that were affected by RA. Results: NF-κB1 and IKKε gene expression levels were significantly increased in cases with positive RF and Anti-CCP compared to patients without (p < 0.001 for both). Also, according to disease activity; the higher the activity the more NF-κB1 and IKKε gene expression levels with significant differences (p <0.001). Higher erythrocyte sedimentation rate (ESR), PDUS, NF-κB1 and IKKε gene expression levels were associated with risk of higher DAS grades in univariable analysis (p=0.007, 0.023, 0.011, 0.002 respectively). However, in multivariable analysis, only higher NF-κB1 and IKKε gene expression levels were considered independent predictors of higher DAS grades (p=0.019, 0.044 respectively). Conclusion: Our findings suggest that NF-κB1 and IKKε play an important role in RA pathogenesis and could be considered as an activity indicator.

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NFKB1 promoter –94 insertion/deletion ATTG polymorphism (rs28362491) is associated with severity and disease progression of rheumatoid arthritis through interleukin-6 levels modulation in Egyptian patients

Cited by 10 publications

References 43 publications

The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis

The influence of the -94 Ins/Del ATTG polymorphism of NFkB on the anti-CCP antibody levels in patients with rheumatoid arthritis

SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

Association of NF-κB1/IKKε Gene Expression with Disease Activity Indices in Patients with Early Rheumatoid Arthritis

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