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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-02-01
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| Series: | Autoimmunity |
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| Online Access: | http://dx.doi.org/10.1080/08916934.2019.1710831 |
| _version_ | 1797684720335585280 |
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| author | Isaura Isabelle Fonseca Gomes da Silva Camilla Albertina Dantas Lima Maria Larissa Andrade Monteiro Daniella Alves Silva Pimentel Barboza Eliezer Rushansky Maria Helena Queiroz de Araújo Mariano Paula Sandrin-Garcia Paulo Roberto Eleutério de Souza Maria de Mascena Diniz Maia |
| author_facet | Isaura Isabelle Fonseca Gomes da Silva Camilla Albertina Dantas Lima Maria Larissa Andrade Monteiro Daniella Alves Silva Pimentel Barboza Eliezer Rushansky Maria Helena Queiroz de Araújo Mariano Paula Sandrin-Garcia Paulo Roberto Eleutério de Souza Maria de Mascena Diniz Maia |
| author_sort | Isaura Isabelle Fonseca Gomes da Silva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:33:49Z |
| format | Article |
| id | doaj.art-1035dae2b3554601bd7443bd2ee21635 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:33:49Z |
| publishDate | 2020-02-01 |
| publisher | Taylor & Francis Group |
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| series | Autoimmunity |
| spelling | doaj.art-1035dae2b3554601bd7443bd2ee216352023-09-15T10:01:08ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2020-02-015329510110.1080/08916934.2019.17108311710831IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot studyIsaura Isabelle Fonseca Gomes da Silva0Camilla Albertina Dantas Lima1Maria Larissa Andrade Monteiro2Daniella Alves Silva Pimentel Barboza3Eliezer Rushansky4Maria Helena Queiroz de Araújo Mariano5Paula Sandrin-Garcia6Paulo Roberto Eleutério de Souza7Maria de Mascena Diniz Maia8Federal University of PernambucoLaboratory of Immunopathology Keizo AsamiFederal Rural University of PernambucoFederal Rural University of PernambucoUniversity of PernambucoUniversity of PernambucoFederal University of PernambucoFederal Rural University of PernambucoFederal Rural University of PernambucoRheumatoid 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.http://dx.doi.org/10.1080/08916934.2019.1710831combined effectpolymorphismrheumatoid arthritissnpgene interaction |
| spellingShingle | Isaura Isabelle Fonseca Gomes da Silva Camilla Albertina Dantas Lima Maria Larissa Andrade Monteiro Daniella Alves Silva Pimentel Barboza Eliezer Rushansky Maria Helena Queiroz de Araújo Mariano Paula Sandrin-Garcia Paulo Roberto Eleutério de Souza Maria de Mascena Diniz Maia IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study Autoimmunity combined effect polymorphism rheumatoid arthritis snp gene interaction |
| title | IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study |
| title_full | IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study |
| title_fullStr | IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study |
| title_full_unstemmed | IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study |
| title_short | IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study |
| title_sort | il1β il18 nfkb1 and ifng gene interactions are associated with severity of rheumatoid arthritis a pilot study |
| topic | combined effect polymorphism rheumatoid arthritis snp gene interaction |
| url | http://dx.doi.org/10.1080/08916934.2019.1710831 |
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