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Toll样受体基因多态性与EBV感染相关胃癌的易感性

赵真真,石源源,刘  颂,王笑峰,罗  兵*   

  1. 山东省青岛大学医学院微生物学教研室,山东  青岛  266021
  • 收稿日期:2014-01-10 修回日期:2014-04-09 出版日期:2014-05-30 发布日期:2014-05-30
  • 通讯作者: 罗 兵,E-mail:qdluobing@163.com
  • 作者简介:赵真真(1987- ),女,山东青岛市人,硕士研究生,研究方向:EBV相关肿瘤。E-mail: qdzzz1987@ gmail.com
  • 基金资助:

    国家自然科学基金(30970157),山东省自然科学基金(ZR2011CM016)

Toll-like receptors gene polymorphism and susceptibility to EBV- associated gastric carcinoma

ZHAO Zhen-zhen,SHI Yuan-yuan,LIU Song,WANG Xiao-feng,LUO Bing*   

  1. Department of Medical Microbiology, Qingdao University Medical College, Qingdao 266021, Shandong, China
  • Received:2014-01-10 Revised:2014-04-09 Online:2014-05-30 Published:2014-05-30

摘要:

目的: 探讨Toll样受体(TLR)家族成员TLR2基因启动子区-196~-174 del和TLR4基因 Thr399Ile位点多态性与EBV相关胃癌(EBVaGC)及EBV阴性胃癌(EBVnGC)易感性的关系。方法:采用PCR技术检测52例EBVaGC,157例EBVnGC以及94例正常对照人群TLR2(-196~-174 del)基因多态性;PCR-限制性片段长度多态性(PCR-RELP)技术检测50例EBVaGC,67例EBVnGC以及71例正常对照TLR4 Thr399Ile位点基因型及等位基因分布;分析2种基因多态性与EBVaGC及EBVnGC易感性的关系。结果:胃癌组与对照组比较TLR2(-196~-174 del)基因型分布无显著差异(χ2=3.180,P=0.075),胃癌组del等位基因频率明显高于对照组(χ2=4.875, P=0.027),del等位基因携带者的罹患危险性明显高于非携带者(OR=1.491,95%CI=1.045~2.126);EBVaGC组和EBVnGC组中,TLR2(-196~-174 del)3种基因型以及del等位基因频率差异无统计学意义(χ2=0.05,P=0.867)。EBVaGC组、EBVnGC组和正常对照组中均未发现TLR4基因Thr399Ile位点的多态,其基因型分布及等位基因频率差异均无统计学意义(P>0.05)。结论:TLR2(-196~-174 del)等位基因可能是胃癌发病危险因素,且在EBVaGC和EBVnGC两种胃癌发生中产生相同的影响。未发现TLR2(-196~-174 del)和TLR4基因Thr399Ile基因型分布与EBVaGC的易感性相关。

关键词: Toll样受体, 胃癌, EB病毒, 基因多态性

Abstract:

OBJECTIVE: To explore the relationship of Toll-like receptors 2 (TLR2) and TLR4 Thr399Ile gene polymorphism and the susceptibility to EBV-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC). METHODS:TLR2 gene promoter region - 196 to - 174 del polymorphism was detected by using the allele-specific polymerase chain reaction in 52 EBVaGCs,157 EBVnGCs and 94 normal controls. TLR4 gene Thr399Ile genotype and allele distribution were evaluated by PCR and restriction fragment length polymorphism (PCR-RFLP) in 50 EBVaGCs,67 EBVnGCs and 71 normal controls. The relationship between gene polymorphism in TLR2 and TLR4 coding genes and the susceptibility to EBVaGC and EBVnGC was analysed. RESULTS:There was no significant difference (χ2=3.180,P=0.075) between gastric cancer group and control group in genotype distribution of TLR2(-196 to -174 del),but the del allele frequency of gastric cancer group was obviously higher than that of control group (χ2=4.875,P=0.027),The risk of developing gastric carcinoma in del allele carriers was significantly higher than that in controls(OR=1.491,95%CI= 1.045-2.126). TLR2 (-196 to -174 del) genotype and the frequency of del allele showed no significant difference in EBVaGC and EBVnGC group (χ2=0.05,P=0.867). TLR4 gene Thr399Ile locus mutation was not found in EBVaGC,EBVnGC or normal control groups. The genotype distribution and allele frequency also revealed no statistical differences . CONCLUSION:TLR2 -196 to - 174 del alleles could be risk factors for gastric carcinoma,but its effects were not different in EBVaGC and EBVnGC. There was no obvious correlation in the genotype distribution of TLR2(-196 to -174 del) and TLR4 gene Thr399Ile and EBVaGC genetic susceptibility.

Key words: Toll-like receptor, gastric carcinoma, EBV, gene polymorphism