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IL-18基因启动子单核苷酸多态性及血清水平与宫颈癌相关性

Correlation of serum IL-18 level and IL-18 gene promoter polymorphisms to the risk of cervical cancer

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【作者】 亓涛王前郑磊杨红玲包杰

【Author】 QI Tao1, WANG Qian1, ZHENG Lei1, YANG Hong-ling2, BAO Jie1 1Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; 2Department of Clinical Laboratory, Guangzhou Maternal and Infant Hospital, Guangzhou 510180, China

【机构】 南方医科大学南方医院检验科广州市妇婴医院检验科南方医科大学南方医院检验科 广东广州510515广东广州510515广东广州510180

【摘要】 目的研究细胞因子白介素-18(IL-18)基因多态性位点以及相应血清IL-18含量与宫颈癌(cervi calcancer,CC)的相关性。方法选择50例宫颈癌患者和50例健康对照作为研究对象,采集外周静脉血,用直接测序法对IL-18基因启动子区rs5744224、rs1946519、rs1946518、rs5744225、rs5744226等5个SNP位点的多态性进行检测,并用双抗体夹心酶联免疫吸附实验(ELISA)法检测血清IL-18含量。结果①5个SNP中有rs1946519(T/G)、rs1946518(A/C)2个SNP位点呈多态性并有连锁关系,以三种基因型存在:TT-AA、GG-CC、TG-AC。患者组3种基因型频率分别为56%(28/50)、10%(5/50)、34%(17/50),对照组3种基因型频率分别18%(9/50)、34%(17/50)、48%(17/50)。两组研究对象基因型的分布频率差异有统计学意义(χ2=17.497,P=0.000)。宫颈癌患者与对照组之间等位基因T(A)、G(C)频率差异有统计学意义(χ2=19.662,P=0.000)。②采用析因设计方差分析,结果显示两组之间血清IL-18平均浓度比较差异有统计学意义(F=14.445,P=0.000);按照2个SNP位点TT-AA、GG-CC、TG-AC三个基因型分为3组,3组的血清IL-18平均浓度差异有统计学意义(F=11.307,P=0.000);宫颈癌患病与否与不同IL-18基因型之间交互效应显著(F=4.223,P=0.018)。结论IL-18基因启动子位点多态性及其血清含量都与宫颈癌相关,rs1946519、rs1946518两个SNP位点多态性影响可能是控制宫颈癌发生发展的重要遗传因素。

【Abstract】 Objective To investigate the correlations of serum interleukin-18 (IL-18) level and IL-18 gene promoter polymorphisms to the development of cervical cancer (CC). Methods Five single nucleotide polymorphisms (SNPs) of the IL-18 gene promoter region at position rs5744224, rs1946519, rs1946518, rs5744225 and rs5744226 were detected by means of sequences analysis in 50 CC patients and 50 normal subjects that matched for age and residence, and their serum IL-18 level was tested using enzyme-linked immunosorbent assay (ELISA). Results Two linkage SNP sites (rs1946519 and rs1946518) in the up-stream of IL-18 gene were identified to present 3 genotypes, namely TT-AA, GG-CC, and TG-AC. A significant difference in the frequency of the 3 genotypes was observed between the CC patients and the normal controls (χ2=17.497, P=0.000). The frequency of T (A)/G (C) alleles was 42% (42/100) in normal controls and 73% (73/100) in patients, showing significant diference (χ2=19.662, P=0.000). Serum IL-18 concentrations of the CC patients was significantly lower than that of the normal controls (95.470±18.827 vs 116.756±16.262 pg/ml, F=14.445, P=0.000). In the cancer patients, serum IL-18 was 90.668±20.363 pg/ml for TT-AA genotype, 119.641±15.338 pg/ml for GG-CC genotype, and 112.793±13.326 pg/ml for TG-AC genotype, showing significant differences (F=11.307, P=0.000). A significant interaction effect was suggested between IL-18 genotype and CC (F=4.223, P=0.018). Conclusion IL-18 gene polymorphisms and serum IL-18 level are related to the development of CC, and two SNPs, rs1946518 and rs1946519, can be important genetic factors for the susceptibility of cervical neoplasms.

【基金】 卫生部科研基金项目(WKJ2007-3-001);广东省人口计生委科研项目(2006027)~~
  • 【文献出处】 南方医科大学学报 ,Journal of Southern Medical University , 编辑部邮箱 ,2008年05期
  • 【分类号】R737.33
  • 【被引频次】10
  • 【下载频次】241
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