白细胞介素-1基因多态性与类风湿关节炎病情活动及骨代谢的相关性

目的 探讨IL－1α和β基因多态性与类风湿关节炎（RA）疾病活动性和骨代谢的相关以及IL－1基因多态性与RA优势基因（motif gene）之间的相关关系。方法 检测了65例RA 患者和60例非风湿病患者的IL－1等位基因分布。IL－1基因多态性分析采用PCR－RFLP方法，HLA－DR分型采用PCR－SSOP方法。Fisher's检验及方差分析被用于基因频率和携带率及临床统计。结果 IL－1α的频率和携带率在RA病人和对照组之间差异无显著性。在女性RA病人IL－1β纯合子等位基因2的出现频率更高，在男性RA病人中等位基因1的频率较高而等位基因2的携带率较低。IL－1β等位基因2携带率与C反应蛋白（CRP）、红细胞沉降率（ESR）、关节痛和骨质密度（BMD）呈相关，与尿脱氧吡啶／肌酐比值（Udpd/Crea）水平及维生素D3水平呈负相关。IL－1α等位基因1与CRP呈负相关，与类风湿因子（RF）和关节肿胀呈正相关。IL－1α等位基因2的出现伴随较高的ESR、健康质量评估积分（HAQ），维生素D3水平和较低的RF滴度、肿胀关和（SJC）和BMD。HLA－DRB1 RA优势等位基因和IL－1β等位基因2的同时出现对RA 的一些临床参数并没有影响。结论 RA与IL－1基因多态性显著相关，特别是IL－1β等位基因2与病 情活动及骨密度增高直接。HLA－DRB1RA优势等位基因和IL－1β等位基因2的同时出现并不预示RA病情更严重。

Correlation between interleukin-1 gene polymorphism and disease activity and bone mineral metabolism in rheumatoid arthritis

Objective　To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism,and whether there is any relationship between IL-1β and RA motif gene.Methods　IL-1 gene polymorphisms were analyzed in 65 RA patients who satisfied ACR criteria and 60 controls.The 2 polymorphisms in each gene for IL-1α－889 and IL-1β＋3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP.Fisher′s test and analysis of variance were used to analyze the data.Results　There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and controls.The β 2/2 genotype of IL-1β was more common in female RA patients compared with controls.A higher carriage rate of IL-1β 1 and low carriage rate of IL-1β 2 occurred in male RA patients.An increased IL-1β 2 carriage was associated with active rheumatoid disease as indicated by a higher CRP,ESR and pain score and a higher BMD,lower vit-D3 and Udpd/Crea level.A higher frequency of IL-1α 1 was associated with a lower CRP value and higher RF and SJC.A higher carriage rate of IL-1α 2 was associated with a higher ESR,HAQ score and vit-D3，but conversely a lower SJC,RF and BMD.The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time was not effective to clinical and laboratory parameters of RA.Conclusion　It is demonstrated that polymorphisms of the IL-1 gene may influence the occurrence of RA.Carriage of IL-1β 2 polymorphisms is associated with more active disease and higher BMD IN RA.The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time does not contribute to disease activity.