切换至 "中华医学电子期刊资源库"
高级检索
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:
全文 ( ) 下载PDF ( ) 导出引用
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]. 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]. 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
[1]
Peach CA, Carr AJ, Loughlin J. Recent advances in the genetic investigation of osteoarthritis[J]. Trends Mol Med, 2005, 11(4):186-191.
[2]
Garstang SV, Stitik TP. Osteoarthritis: epidemiology, risk factors, and pathophysiology[J]. Am J Phy Med Rehabil, 2006, 85(11):S2-S11.
[3]
Steinmeyer J. Cytokines in osteoarthritis-current status on the pharmacological intervention[J]. Front Biosci, 2004, 9(9):575-580.
[4]
Loughlin J. The genetic epidemiology of human primary osteoarthritis: current status[J]. Expert Rev Mol Med, 2005, 7(9):1-12.
[5]
Towne JB. IL-1F6，IL-1F8，and IL-1F9，signal throughIL-1RrD2 andIL-1RAcP to activatethel athway1eading to NF kappaB and MAP[J]. Eiol Cbem, 2014, 279(14):13677-13688.
[6]
He W, Pelletier JP, Martel-Pelletier J, et al. Synthesis of interleukin 1beta, tumor necrosis factor-alpha, and interstitial collagenase (MMP-1) is eicosanoid dependent in human osteoarthritis synovial membrane explants: interactions with antiinflammatory cytokines[J]. J Rheumatol, 2002, 29(3):546-553.
[7]
Hajizadeh YS, Emami E, Nottagh M, et al. Effects of interleukin-1 receptor antagonist (IL-1Ra) gene 86 bp VNTR polymorphism on recurrent pregnancy loss: a case-control study[J]. Horm Mol Biol Clin Investig, 2017, 30(3):1868-1891.
[8]
Kayar NA, Alptekin NÖ, Erdal ME. Interleukin-1 receptor antagonist gene polymorphism, adverse pregnancy outcome and periodontitis in Turkish women[J]. Arch Oral Biol, 2015, 60(12):1777-1783.
[9]
Kristy LW, Jevseva DS. AAOS clinical practice guideline：surgical management of osteoarthritis of the knee[J]. J Am Acad Orthop Surg, 2016, 24(8):e94-e96.
[10]
Bhattacharya R, Kumar V, Safawi E, et al. The knee skyline radiograph: its usefulness in the diagnosis of patello-femoral osteoarthritis[J]. Int Orthop, 2007, 31(2):247-252.
[11]
Patel R, Dwivedi M, Mansuri MS, et al. Association of neuropeptide-Y (NPY) and interleukin-1beta (IL1B), genotype-phenotype correlation and plasma lipids with type-II diabetes[J/OL]. PLoS One, 2016, 11(10):e0164437.

URL    
[12]
Tabrez S, Jabir NR, Firoz CK, et al. Estimation of interleukin-1β promoter (-31 C/T and -511 T/C) polymorphisms and its level in coronary artery disease patients[J]. J Cell Biochem, 2017, 118(9):2977-2982.
[13]
Szpecht D, Gadzinowski J, Nowak I, et al. The significance of IL-1β ＋3953C>T, IL-6 -174G>C and -596G>A, TNF-α -308G>A gene polymorphisms and 86 bp variable number tandem repeat polymorphism of IL-1RN in bronchopulmonary dysplasia in infants born before 32 weeks of gestation[J]. Cent Eur J Immunol, 2017, 42(3):287-293.
[14]
Cai H, Sun HJ, Wang YH, et al. Relationships of common polymorphisms in IL-6, IL-1A, and IL-1B genes with susceptibility to osteoarthritis: a meta-analysis[J]. Clin Rheumatol, 2015, 34(8):1443-1453.
[15]
Towne JE, Crka KE, Renshaw BR, et al. Interleukin(IL)-1F6，II-1F8，and IL-1F9，signal through IL-1RrD2 and IL-1RAcP to activatethel athway1eading to NF kappaB and MAPKs[J]. J Eiol Chem, 2004, 279(14):13677-13688.
[16]
Smith AJ, Keen LJ, Billingham MJ, et al. Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis[J]. Genes Immun, 2004, 5(6):451-460.
[17]
Leppävuori J, Kujala U, Kinnunen J, et al. Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locus on 2q[J]. Am J Hum Genet, 1999, 65(4):1060-1067.
[18]
Forster T, Chapman K, Marcelline L, et al. Finer linkage mapping of primary osteoarthritis susceptibility loci on chromosomes 4 and 16 in families with affected women[J]. Arthritis Rheum, 2004, 50(1):98-102.
[19]
Hamajima N, Matsuo K, Saito T, et al. Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection[J]. Jpn J Cancer Res, 2001, 92(4):383-389.
[20]
El-Omar EM, Carrington M, Chow WH, et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer[J]. Nature, 2000, 404(6776):398-402.
[21]
Xu CF, Lewis K, Cantone KL, et al. Effectiveness of computational methods in haplotype prediction[J]. Hum Genet, 2002, 110(2):148-156.
[22]
Meulenbelt I, Seymour AB, Nieuwland M, et al. Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip[J]. Arthritis Rheum, 2004, 50(4):1179-1186.
[23]
Hall SK, Perregaux DG, Gabel CA, et al. Correlation of polymorphic variation in the promoter region of the interleukin-1 beta gene with secretion of interleukin-1 beta protein[J]. Arthritis Rheum, 2004, 50(6):1976-1983.
[24]
Moos V, Rudwaleit M, Herzog V, et al. Association of genotypes affecting the expression of interleukin-1beta or interleukin-1 receptor antagonist with osteoarthritis[J]. Arthritis Rheum, 2000, 43(11):2417-2422.
[25]
Kanoh T, Hasegawa Y, Masui T, et al. Interleukin-1beta gene polymorphism associated with radiographic signs of osteoarthritis of the knee[J]. J Orthop Sci, 2008, 13(2):97-100.
[26]
Colotta F, Dower Sk, Sims JE，et al The type II'decoy' receptor: a novel regulatory pathway for interleukin-1 [J]．Immunol Tod，1994，15(12):562-566.
[27]
Peat E, Thomas D, Duncan L, et al. Clinical classification criteria for knee 0steoarthritis：performance in the general population primary care[J]. Ann Rheum Dis, 2006, 65(4):1363-1367.
[28]
Wang WZ, Guo X, Duan C, et al. Comparative analysis of gene expression profiles between the normal human cartilage and one with endemic osteoarthritis[J]. Osteoarthritis Cartilage, 2009, 17(6):83-89.
[29]
Swellam M, Mahmoud MS, Samy N, et al. Potential influence of interleukin-1 receptor antagonist gene polymorphism on knee osteoarthritis risk[J]. Dis Markers, 2010, 28(5):299-305.
[30]
王友成，刘铮，刘国华，等．TGF-β1基因C1348-T位点与膝骨关节炎的关系[J/CD]．中华关节外科杂志(电子版)，2015，9(4):500-504.
[1] 闫文, 谢兴文, 顾玉彪, 雷宁波, 马成, 于文霞, 高亚雄, 张磊. 微小RNA与全膝关节置换术后深静脉血栓的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(06): 842-846.
[2] 樊绪国, 赵永刚, 杨砚伟. 腓骨在膝骨关节炎作用的研究观点[J]. 中华关节外科杂志(电子版), 2023, 17(06): 855-859.
[3] 李善武, 叶永杰, 王兵, 王子呓, 银毅, 孙官军, 张大刚. 胫骨高位截骨与单髁置换的早期疗效比较[J]. 中华关节外科杂志(电子版), 2023, 17(06): 882-888.
[4] 刘伦, 王云鹭, 李锡勇, 韩鹏飞, 张鹏, 李晓东. 机器人辅助膝关节单髁置换术的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 715-721.
[5] 张中斌, 付琨朋, 朱凯, 张玉, 李华. 胫骨高位截骨术与富血小板血浆治疗膝骨关节炎的疗效[J]. 中华关节外科杂志(电子版), 2023, 17(05): 633-641.
[6] 陈宏兴, 张立军, 张勇, 李虎, 周驰, 凡一诺. 膝骨关节炎关节镜清理术后中药外用疗效的Meta分析[J]. 中华关节外科杂志(电子版), 2023, 17(05): 663-672.
[7] 王岩, 马剑雄, 郎爽, 董本超, 田爱现, 李岩, 孙磊, 靳洪震, 卢斌, 王颖, 柏豪豪, 马信龙. 外泌体在骨质疏松症诊疗中应用的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 673-678.
[8] 赵之栋, 李众利. 骨关节炎早期诊治的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(05): 689-693.
[9] 胡银华, 薛龙. 中国中老年人症状性膝骨关节炎的发病率及危险因素[J]. 中华关节外科杂志(电子版), 2023, 17(04): 470-478.
[10] 利洪艺, 杨浪, 温国洪, 关鸿, 茹江英, 王湘江. 全膝股骨假体矢状面位置与术后膝前痛及功能的关系[J]. 中华关节外科杂志(电子版), 2023, 17(04): 479-484.
[11] 闫兆龙, 张镇斌, 李广兴, 赵璋, 张业勇, 殷鲁旭, 李树锋. 胫骨高位截骨术治疗膝骨关节炎的早期效果及影响因素[J]. 中华关节外科杂志(电子版), 2023, 17(04): 492-499.
[12] 徐燕群, 李平, 杨兴, 薛慧. 脂多糖通过促进透明质酸受体CD44向核转移介导牙周膜细胞白细胞介素6释放[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 335-344.
[13] 王旭, 师绍敏, 毛燕, 季上, 刘亚玲. 肝酶代谢与骨关节炎相关性的研究进展[J]. 中华老年骨科与康复电子杂志, 2023, 09(06): 379-384.
[14] 周晓强, 孙超, 虞宵, 金宇杰, 李志强, 张向鑫, 陈广祥. 同一患者同期行全膝和单髁置换术的早期临床疗效[J]. 中华老年骨科与康复电子杂志, 2023, 09(05): 275-281.
[15] 马聪, 李雪靖, 郑晓佐, 张晓阳, 段坤峰, 刘国强, 郄素会. 关节腔内注射富血小板血浆与透明质酸钠治疗Ⅰ-Ⅲ期膝骨关节炎的对比研究[J]. 中华老年骨科与康复电子杂志, 2023, 09(05): 282-288.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号