IL-1基因多态性对类风湿关节炎病情及IL-1蛋白表达影响

Relationship between IL-1 gene polymorphism and severity of rheumatoid arthritis and secretion of IL-1

目的 :探讨白细胞介素 - 1α(IL - 1α)和白细胞介素 - 1β(IL - 1β)基因多态性对类风湿关节炎 (RA)病情及对IL - 1β产生的影响。方法 :检测 13 6例RA病人及 10 2例正常人的IL - 1等位基因分布 ,其中 72例病人系已明确患病 2年内出现关节破坏者 ,IL - 1基因多态性检测采用PCR -RFLP法 ,同时分析不同类型基因型病人外周血单个核细胞受刺激后分泌IL - 1β水平的不同。结果 :IL - 1α等位基因 1、2的频率和携带率在RA组及正常人组无显著差异。IL - 1β纯合子等位基因 2频率在 2年内出现骨侵蚀组明显高于 2年内未出现骨侵蚀组 ,IL - 1β纯合子等位基因 2携带病人组具有较高的血沉及关节肿胀、压痛指数 ,从携带IL - 1β纯合子等位基因 2病人中分离出的外周血单个核细胞经脂多糖刺激后分泌的IL - 1β量明显高于其它组病人。结论 :RA与IL - 1β基因多态显著相关 ,IL - 1β等位基因 2促进IL - 1β分泌 ,IL - 1β等位基因 2的检测可作为预测RA严重性的一个有用指标。

AIM: To determine the influence of interleukin-1α(IL-1α) and β(IL-1β) gene polymorphisms on rheumatoid arthritis(RA) disease severity and secretion of IL-1β. METHODS: The study included 136 RA patients and 102 healthy controls. PCR-RFLP was used to detect site mutation at IL-1 gene. Meanwhile the IL-1β was also measured in the supernatant of the cultured and stimulated peripheral blood mononuclear cells(PBMC). RESULTS: No difference in the allele frequencies or genotypes of the IL-1α gene polymorphisms was found between the controls and RA patients.IL-1β allele 2 was overrepresented in patients with erosive RA but not in nonerosive patients. The patients with IL-1β allele 2 had a higher swollen joint index, higher tender joint index and erythrocyte sedimentation rate than those without IL-1β allele 2.The IL-1β in supernatant of stimulated PBMC from patients with IL-1β allele 2 had a higher level than that from those without allele 2. CONCLUSION: IL-1 gene polymorphisms may influence the occurrence of RA. Detection of IL-1β allele 2 have a potential prognostic value in RA.