白细胞介素1B和1RN基因多态性与骨关节炎易感性的关系

Association between genetic polymorphisms of interleukin-1 B and interleukin-1 receptor antagonist genes and susceptibility to osteoarthritis

目的在中国青岛地区膝骨性关节炎患者中,探讨白细胞介素-1B(-31C/T、-511C/T、+3954C/T)及其拮抗基因IL-1RN基因多态性与骨关节炎易感性的关系。方法采用病例对照研究,对就诊青岛市胶州中心医院经临床诊断为膝关节骨关节炎的216例患者和233例年龄、性别匹配的健康对照者,排除既往有膝关节外伤史、类风湿性关节炎及合并其他内科疾病的患者,以聚合酶链反应和限制性片段长度多态性(PCR-RFLP)方法检测IL-1B的-31C/T、-511C/T、+3954 C/T位点及IL-1RN的多态性,采用logistic回归分析方法比较不同基因型与骨关节炎发病风险的关系。结果骨关节炎组中IL-1B-511CT、IL-1B+3954CT基因型频率明显高于对照组,与对照组差异有统计学意义(IL-1B-511CT2=2. 034,P=0. 026; IL-1B+3954CT2=5. 526,P=0. 017),IL-1B+3954C/T位点未发现TT基因型,通过logistic回归分析,结果显示与野生型的纯合子相比,杂合子-511CT、+3954CT基因型与骨性关节炎高风险发病率具有相关性[IL-1B-511CT,OR=1. 89,95%CI(0. 56,1. 39),P=0. 026; IL-1B+3954CT,OR=2. 51,95%CI(1. 18,5. 35),P=0. 017]。骨关节炎组和对照组在IL-1B-31C/T位点及IL-1RN基因型分布未见明显差异。结论 IL-1B-511TC、+3954CT基因型人群可能增加对膝骨关节炎的易感性,而IL-1B-31C/T,IL-1RN*2基因多态性可能与膝骨关节炎遗传易感性不具相关性。

Objective To investigate the association between genetic polymorphisms of interleukin-1 B(-31C/T、-511C/T、+3954C/T)and interleukin-1 receptor antagonist(IL-1ra)(gene code:IL-1RN)and susceptibility to knee osteoarthritis patients from Qingdao area of China.Methods A case-control study was conducted in 216 knee osteoarthritis patients from Jiaozhou Central Hospital of Qingdao;previous knee trauma,rheumatoid arthritis and other medical diseases were excluded and 233 healthy controls were matched in age and sex.The single nucleotide polymerphisms(SNPs)at positions IL-1B-31C/T、-511C/T、+3954C/T and IL-1RN were analyzed using polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)and association between genotypes and risk of osteoarthritis were determined by logistic regression analysis.Results An increased frequency of IL-1B-511CT and IL-1B+3954CT genotypes was noted in osteoarthritis patients and the difference was statistically significant compared with the control group[IL-1B-511CT x^2=2.034,P=0.026;IL-1B+3954CT x^2=5.526,P=0.017).No IL-1B+3954TT genotype was found in this study.In a logistic regression analysis,IL-1B-511CT and IL-1B+3954CT genotypes were associated with an odds ratio for osteoarthritis[IL-1B-511CT,OR=1.89,95%CI(0.56,1.39),P=0.026;IL-1B+3954CT,OR=2.51,95%CI(1.18,5.35),P=0.017].No significant difference was found in the allelic or genotypic frequencies of IL-1B-31C/T or IL-1 RN between the osteoarthritis patients and the controls.Conclusion IL-1B-511CT and+3954CT genotypes may associate with an increased risk of knee osteoarthritis,while there is no association between genetic polymorphisms of IL-1B-31C/T and IL-1 RN*2 and susceptibility to knee osteoarthritis.