MMP-2、TIMP-2基因启动子区多态性与NHL临床特点及预后的关系  

Association of SNPs in matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 promoter region with non-Hodgkin’s lymphoma

作　　者：武莉丽[1] 高玉环[1] 李涛[2] 刘丽宏[1] 刘海生[1] 赵桂敏[1] 刁兰萍[1] 

机构地区：[1]河北医科大学第四医院,石家庄050000 [2]河北医科大学流行病与统计教研室

出　　处：《山东医药》2013年第18期1-5,共5页Shandong Medical Journal

基　　金：河北省普通高校强势特色学科项目(200552);河北省卫生厅医学科学研究重点课题计划项目(20120366)

摘　　要：目的研究基质金属蛋白酶-2(MMP-2)和金属蛋白酶组织抑制剂-2(TIMP-2)基因启动子区单核苷酸多态性(SNPs)与非霍奇金淋巴瘤(NHL)临床特点和预后的关系。方法 NHL患者575例采用聚合酶链反应—限制性片段长度多态性(PCR-RFLP)方法检测MMP-2-1306C/T、-735C/T和TIMP-2-418G/C 3个SNPs的基因型分布,分析其与NHL发病风险及临床病理参数的关系。结果 MMP-2-1306C/T和-735C/T的C/C基因型及TIMP-2-418G/C的G/G基因型分布频率较高,分别为69.74%、63.66%和65.22%,符合Hardy-Weinberg平衡(P分别为0.110、0.385、0.677)。Ann Arbor分期Ⅲ、Ⅳ期者-735C/T的C/T、TT+CT基因型和T等位基因分布频率较Ⅰ、Ⅱ期显著增高(P均<0.05)。骨髓浸润NHL患者-1306C/T的T/T基因型分布频率低于C/C基因型(P<0.05)。肿瘤最大直径>5 cm者较≤5 cm者-1306C/T的C/T、T/T、CT+TT基因型、T等位基因及-1306C/-735T单体型分布频率显著降低(P均<0.05);-735C/T的T/T基因型在肿瘤最大直径>5 cm者中的分布频率较≤5 cm者显著升高(P<0.05)。有B症状者-1306T/-735C和-1306C/-735C单体型分布频率显著低于无B症状者(P均<0.05)。MMP-2-735C/T的T/T基因型者较C/C和C/T基因型者3年总生存率显著下降(P均<0.05)。结论 MMP-2和TIMP-2基因启动子区多态性可能与NHL的易感性有关。Objective To investigate the clinical features and prognostic relationship between the single nucleotide polymorphisms（SNPs） in matrix metalloproteinases-2（MMP-2） and tissue inhibitors of metalloproteinase-2（TIMP-2） promoter region and non-Hodgkin’s lymphoma（NHL）.Methods A retrospective study of non-Hodgkin’s lymphoma（NHL） in 575 patients was conducted.Three polymorphisms [MMP-2（-1306C/T and-735C/T） and TIMP-2 gene（-418G/C） ] were analyzed by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method.The possible correlations between the three polymorphisms and clinical pathological parameters in patients with NHL were examined.Results The distribution frequencies of the CC genotypes in MMP-2-1306 C/T and-735C/T and GG genotype in TIMP-2 418 G/C were higher（69.74%,63.66% and 65.22%,respectively）,and within the range of Hardy-Weinberg equilibrium（P = 0.110,0.385 and 0.677,respectively）.The incidence of the CT,TT ＋ CT genotypes and T allele of-735C/T was significantly higher in stage Ⅲ and Ⅳ patients compared to stageⅠand Ⅱpatients（all P 0.05）.The TT genotype of the-1306C/T gene was significantly less frequent compared to CC genotype in bone marrow infiltration cases（P 0.05）.The CT,TT,CT ＋ TT genotypes and T allele in patients exhibiting the-1306C/T polymorphism were significantly less frequent in patients with a large tumor size compared to a smaller tumor（all P 0.05）.The incidence of the TT genotype of the-735C/T polymorphism was significantly higher in patients with a large tumor compared to those with a smaller tumor （P 0.05）.The frequency of the-1306C/-735T haplotype in patients with a smaller tumor size was significantly higher compared to patients with a large tumor（P 0.05）.The-1306T/-735C and-1306C/-735C haplotypes were significantly less frequent in patients with B-symptoms compared to those without（all P 0.05）.Interestingly,patients with the TT genotype of-735C/T exhibited a lower rate of survival（Lo

关 键 词：非霍奇金淋巴瘤 基质金属蛋白酶 金属蛋白酶组织抑制剂 单核苷酸多态性 

分 类 号：R551.2[医药卫生—血液循环系统疾病]