IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different e...

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Published in:	Autoimmunity (Chur, Switzerland) Vol. 53; no. 2; pp. 95 - 101
Main Authors:	Gomes da Silva, Isaura Isabelle Fonseca, Lima, Camilla Albertina Dantas, Monteiro, Maria Larissa Andrade, Barboza, Daniella Alves Silva Pimentel, Rushansky, Eliezer, Mariano, Maria Helena Queiroz de Araújo, Sandrin-Garcia, Paula, de Souza, Paulo Roberto Eleutério, Maia, Maria de Mascena Diniz
Format:	Journal Article
Language:	English
Published:	England Taylor & Francis 17-02-2020 Taylor & Francis Group
Subjects:	Adult Alleles Amplified Fragment Length Polymorphism Analysis Arthritis, Rheumatoid - complications Arthritis, Rheumatoid - diagnosis Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - immunology Biomarkers - analysis Case-Control Studies Combined effect Disability Evaluation Female Gene Frequency gene interaction Genetic Predisposition to Disease Healthy Volunteers Humans Interferon-gamma - genetics Interleukin-18 - genetics Interleukin-1beta - genetics Male Middle Aged NF-kappa B p50 Subunit - genetics Pilot Projects polymorphism Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide Protective Factors rheumatoid arthritis Risk Factors Severity of Illness Index SNP gene interaction polymorphism SNP Combined effect rheumatoid arthritis
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Summary:	Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1β, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1β (rs1143634), -137 G/C IL18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1β (rs1143634), -137 G/C IL-18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23
ISSN:	0891-6934 1607-842X
DOI:	10.1080/08916934.2019.1710831