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.

中文翻译：

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IL1β，IL18，NFKB1和IFNG基因相互作用与类风湿关节炎的严重程度有关：一项前瞻性研究。

类风湿关节炎（RA）是一种自身免疫性疾病，可导致进行性和功能性残疾。文献资料表明，RA患者某些炎症蛋白失调，其遗传多态性可能与不同种族的疾病的病因和发病机理有关。在不同RA人群中研究了IL1β，IL18，NFKB1和IFNG基因的多态性，但分析结果相矛盾。因此，我们假设这些基因的多态性可能对疾病的易感性和严重性具有综合影响。我们评估了巴西东北部人群中的+3953 C / TIL1β（rs1143634），-137 G / C IL18（rs187238），-94 ins / del ATTG NFKB1（rs28362491）和+874 T / A IFNG（rs2430561）多态性。收集外周血样品并进行DNA提取。通过RFLP和ARMS-PCR评估多态性。在rs1143634中观察到一种关联，该关联在T等位基因的携带者中显示出对RA发育的保护作用（OR = 0.58； 95％CI 0.36-0.92； p = .020）。此外，我们发现具有HAQ指数（p = .021）的rs1143634基因型与具有DAS28（p = .029）和CDAI（p = .029）的rs2430561基因型之间存在关联。关于这些SNP的综合作用（C / C到rs1143634，G / G到rs187238，I / I到rs28362491和AA到rs2430561），我们发现功能性残疾减少（HAQ指数p <.001）和ESR显着相关（p = .034），表明这些基因型携带者的疾病活动性较低。GLM分析证实了这些关联（HAQ（F = 5.497; p <.001）和ESR（F = 2.727; p =。032））。我们的分析表明，在研究人群中，+ 3953 C / TIL-1β（rs1143634），-137 G / C IL-18（rs187238），-94 ins / del ATTG NFKB1（rs28362491）和+874 T / A IFNG（ rs2430561）多态性虽然不会单独影响疾病，但可共同导致RA严重程度。