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中华关节外科杂志(电子版)

中华关节外科杂志(电子版) ›› 2018, Vol. 12 ›› Issue (04) : 516 -522. doi: 10.3877/cma.j.issn.1674-134X.2018.04.013

所属专题： 文献；

临床论著

白细胞介素1B和1RN基因多态性与骨关节炎易感性的关系
申成凯1, 赵希春1, 孙代同1, 赵军强1, 陈燕1, 赵海军1, 吕成昱2,†()   
  1. 1. 266300　青岛市胶州中心医院关节创伤外科
    2. 266003　青岛大学附属医院关节外科
  • 收稿日期:2018-01-28 出版日期:2018-08-01
  • 通信作者: 吕成昱
  • 基金资助:
    青岛市卫生科技计划项目(2015－WJZD072)

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

Chengkai Shen1, Xichun Zhao1, Daitong Sun1, Junqiang Zhao1, Yan Chen1, Haijun Zhao1, Chengyu Lyv2,†()   

  1. 1. Joint Trauma Surgery Jiaozhou center hospital of Qingdao, Qingdao 266300, China
    2. Joint Surgery The Affiliated Hospital of Medical College, Qingdao Univercity, Qingdao 266003, China
  • Received:2018-01-28 Published:2018-08-01
  • Corresponding author: Chengyu Lyv
  • About author:
    Corresponding author: Lyv Chengyu, Email:
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引用本文：

申成凯, 赵希春, 孙代同, 赵军强, 陈燕, 赵海军, 吕成昱. 白细胞介素1B和1RN基因多态性与骨关节炎易感性的关系[J/OL]. 中华关节外科杂志(电子版), 2018, 12(04): 516-522.

Chengkai Shen, Xichun Zhao, Daitong Sun, Junqiang Zhao, Yan Chen, Haijun Zhao, Chengyu Lyv. Association between genetic polymorphisms of interleukin-1 B and interleukin-1 receptor antagonist genes and susceptibility to osteoarthritis[J/OL]. Chinese Journal of Joint Surgery(Electronic Edition), 2018, 12(04): 516-522.

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 χ2＝2.034，P＝0.026；IL-1B＋3954CT χ2＝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。

关键词: 骨关节炎, 多态现象，遗传, 白细胞介素
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 χ2=2.034, P=0.026; IL-1B+ 3954CT χ2=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.

Key words: Osteoarthritis, Polymorphism, genetic, Interleukins
图1 IL(白介素)-1-511C/T位点基因分型的电泳结果。分析IL-1-511C/T多态性的PCR-RFLR(聚合酶链反应－限制性片段长度多态性)检测：泳道2、4、8为纯合子CC基因型(90 bp和114 bp两条切片段)。泳道5、6、7、9为杂合子CT基因型，(304 bp、190 bp和114 bp 3条片段)，而等位基因T没有产生切割片段，泳道1、3为纯合子TT基因型，(304为1条片段)
图2 IL(白介素)-1＋3954C/T位点基因分型的电泳结果。分析IL-1＋3954C/T多态性的PCR-RFLR(聚合酶链反应－限制性片段长度多态性)检测，泳道2、3、4、5为纯合子CC基因型(135 bp和114 bp两条片段)。泳道1、6为杂合子CT基因型，(249 bp、135 bp和114 bp 3条片段)
图3 IL(白介素)-1-31C/T位点基因分型的电泳结果。分析IL-1-31C/T多态性的PCR-RFLR(聚合酶链反应－限制性片段长度多态性)检测，泳道6为纯合子TT基因型(150 bp和84 bp两条片段)。泳道1、7为杂合子CT基因型(234 bp、150 bp和84 bp 3条片段)，而等位基因C没有产生切割片段，泳道2、3、4、5为纯合子CC基因型，(234 bp 1条片段)
图4 IL(白介素)-1RN位点基因分型的电泳结果。分析IL-1RN多态性的PCR-RFLR(聚合酶链反应－限制性片段长度多态性)检测，泳道1、4、5为1/1型(1条410 bp的片段)，泳道2、6为1/2型(410 bp和240 bp两条片段)，泳道9为1/4型(410 bp和325 bp两条片段)，泳道3、7位2/2型(1条240 bp的片段)
表1 骨关节炎组和对照组的人口统计数据
? 例数 年龄[岁，(±s)] 性别(男/女) BMI[kg/m2，(±s)]
对照组 233 55.7±13.5 54/179 25.3±1.3
骨关节炎组 216 56.4±14.3 48/168 26.4±1.3
统计值 ? t＝1.519 χ2＝0.352 t＝2.643
P值 ? >0.05 >0.05 >0.05
表2 骨关节炎组和对照组基因型的H-W平衡分析
基因位点 ? 骨关节炎组(n＝216) 对照组(n＝233)
? 观察值 理论值 观察值 理论值
IL-1B-31 T/C CC 49 46.3 54 50.8
? CT 101 96.1 109 115.4
? TT 66 73.6 70 66.8
P值 ? 0.780 ? 0.835 ?
IL-1B-511 C/T CC 56 53.1 59 58.3
? CT 105 106.8 92 99.4
? TT 55 56.1 82 75.3
P值 ? 0.638 ? 0.454 ?
IL-1B＋ 3594 C/T CC 169 169.5 207 205.3
? CT 47 45 26 27.2
? TT 0 1.3 0 0.9
P值 ? 0.742 ? 0.619 ?
IL-1RN VNTR 1/1 158 157.5 169 168
? 1/2 45 54 50 55.8
? 2/2 8 4.5 10 9.2
? 1/3 0 0 0 0
? 1/4 5 0 4 0
P值 ? 0.092 ? 0.135 ?
表3 两组IL-1B基因型频率的分布差异及基因型与骨关节炎风险性非条件Logistic回归分析(±s)
分组 例数 IL-1B-31 T/C [例(%)]
TT CT CC 等位基因T
骨关节炎组 216 49(22.6) 101(46.8) 66(30.6) 199(46.1)
对照组 233 54(23.2) 109(46.7) 70(30.1) 217(46.7)
OR(95%可信区间) ? 1.00 1.06(0.69，1.66) 0.95(0.57，1.59) ?
χ2值 ? ? 0.216 ? ?
P值 ? ? 0.121a ? 0.715b
分组 例数 IL-1B-511 T/C [例(%)]
TT CT CC 等位基因T
骨关节炎组 216 56(25.9) 105(48.6) 55(24.5) 217(50.2)
对照组 233 59 (25.3) 92 (39.5) 82(35.2) 206(44.2)
OR(95%可信区间) ? 1.00 1.89(0.56，1.39) 0.87(0.52－1.46) ?
χ2值 ? ? 2.034 ? ?
P值 ? ? 0.026c ? 0.957d
分组 例数 IL-1B＋3954T/C [例(%)]
TT CT CC 等位基因T
骨关节炎组 216 169(78.2) 47(21.8) 0 47(10.9)
对照组 233 207(88.9) 26(11.1) 0 26(5.6)
OR(95%可信区间) ? ? 1.00 2.51(1.18，5.35) ?
χ2值 ? 5.526
P值 ? ? 0.017e ? 0.041f
表4 两组IL-1RN基因型频率的分布差异及基因型与骨关节炎风险性非条件Logistic回归分析
基因型 骨关节炎组(例) 对照组(例) OR(95%可信区间) χ2 P值
1/1 158 169 1.00 ? ?
1/2 45 50 1.35(0.81，2.42) ? ?
2/2 8 10 2.49(0.56，12.47) ? ?
1/3 0 0 0.00 ? ?
1/4 5 4 1.96(0.31，9.43) 0.800 0.992a
1/1＋1/3＋1/4 163 173 1.00 ? ?
1/2＋2/2 53 60 2.35(1.05，5.27) 0.833 0.316b
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