中国血液净化

中国血液净化 ›› 2014, Vol. 13 ›› Issue (07): 515-519.doi: 10.3969/j.issn.1671-4091.2014.07.008

• 临床研究 • 上一篇    下一篇

糖尿病肾病患者CX3CR1基因V249I多态性与炎症介质的关系

方亚君1,朱阿楠1,许红1,王利峰2,陈红宇3   

  1. 1. 浙江省余姚市中医医院内科  2. 浙江省余姚市中医医院血透室  3.浙江省余姚市中医医院肾内科  
  • 收稿日期:2014-01-26 修回日期:2014-05-07 出版日期:2014-07-12 发布日期:2014-07-12
  • 通讯作者: 方亚君 fyj_yy@126.com E-mail:fyj_yy@126.com
  • 基金资助:

    浙江省余姚市科技局项目(No. 2009Y11)

Relationship between V249I polymorphism in CX3CR1 gene and inflammatory mediators in diabetic nephropathy

  • Received:2014-01-26 Revised:2014-05-07 Online:2014-07-12 Published:2014-07-12
  • Supported by:

    Fractalkine|CX3CR1 gene| Gene polymorphism|Diabetic nephropathy|Inflammation mediator

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摘要： 目的研究糖尿病肾病患者Fractalkine(FKN)受体CX3CR1 基因V249I 多态性与炎症介质NF-κb、FKN、IL-6、TNF-α的关系。方法应用聚合酶链反应限制片段长度多态性方法及测序法对80 例糖尿病肾病(DN 组)患者、119 例糖尿病(DM 组)患者和118 例对照者(C 组)的CX3CR1 基因多态性进行分析，同时检测各组血清中NF-κb 、FKN、IL- 6、TNF-α含量。结果等位基因249I 在对照组(20.33%)中的分布频率明显高于DN 组(17.23%)和DM 组(8.75%)(χ2=9.698，P=0.002)；血清中NF-κb、FKN、IL-6、TNF-α含量DN 组高于DM 组，DM 组高于C 组，差异均有统计学意义(各指标F 值分别为23.318、52.507、8.821、12.013；P 值分别为0.000、0.000、0.001、0.000)；DN 组及DM 组中VI+II 基因型FKN 含量较VV 基因型FKN 含量明显增加(F=21.216；P=0.000)；DN 组及DM 组中VI+II 基因型NF-κB 含量较VV 基因型含量明显减少(F=15.361；P=0.000)；各组不同基因型中IL- 6 的含量并无显著差异(F=1.387；P=0.053)。结论FKN 受体CX3CR1 等位基因V249I 变异可能与糖尿病肾病的发病危险性下降有关;CX3CR1 多态性有可能通过影响肾脏的炎症过程而参与DN 的发生发展。

关键词: 趋化因子受体, CX3CR1, V249I, 基因多态性, 糖尿病肾病, 炎症介质

Abstract: Objective To investigate the relationship between the polymorphism in fractalkine receptor CX3CR1 gene and inflammation mediators including NF-κB, FKN, IL-6 and TNF-α in diabetic nephropathy (DN) patients. Methods By polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP) and sequencing methods, the V249I polymorphism in CX3CR1 gene was determined in 80 DN patients, 119 diabetes mellitus (DM) patients and 118 control individuals. The genotype frequency of V249I polymorphism in CX3CR1 gene was compared among the groups. Serum levels of NF-κB, FKN, IL-6, and TNF-α were measured. Results The allele frequency of V249I polymorphism was higher in control group (20.33%) than in DN group (8.75%; χ2=9.698, P=0.002) and DM group (17.23%; P< 0.05). Serum levels of NF-κB, FKN, IL-6, TNF-α were higher in DN group than in DM and were higher in DM group than in control group (F=23.318, P<0.001 for NF-κB; F=52.507, P<0.001 for FKN; F=8.821, P=0.001 for IL-6; F=12.013, P＜0.001 for TNF-α). In the DN and DM groups, serum FKN increased significantly in patients carrying V/I or I/I genotype than those carrying V/V genotype (F=21.216; P=0.000); serum NF-κB decreased obviously in those carrying V/I or I/I genotype than those carrying V/V genotype (F=15.361; P=0.000); serum IL-6 was unchanged among the patients carrying different genotypes (V/I, I/I and V/V genotypes) (F=1.387; P=0.053). Conclusion The V249I allele in fractalkine receptor CX3CR1 gene may associate with a lower risk of diabetic
nephropathy. This polymorphism in CX3CR1 gene may be involved in the pathogenesis of DN through involving inflammation processes.