MMP-2和TIMP-2基因启动子区多态性与侵袭性T细胞淋巴瘤关系的研究  

Clinical impact of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in aggressive T-cell lymphoma

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

机构地区：[1]河北医科大学第四医院血液内科,河北石家庄050000 [2]河北医科大学流行病与统计教研室,河北石家庄050017

出　　处：《中国现代医学杂志》2013年第35期50-57,共8页China Journal of Modern Medicine

基　　金：河北省卫生厅医学科学研究重点课题计划项目(No: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）与侵袭性T细胞淋巴瘤临床特点和预后的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测192例侵袭性T细胞淋巴瘤患者MMP-2-1306C/T、-735C/T和TIMP-2-418G/C 3个SNPs的基因型。结果①MMP-2-1306C/T和-735C/T的TT基因型及TIMP-2-418G/C的CG基因型分布频率显著升高,分别为69.44%、59.82%和48.04%,分布符合Hardy-Weinberg平衡（P=0.105,P=0.297,P=0.203）。②MMP-2-1306C/T、-735C/T和TIMP-2-418G/C的基因型分布频率与侵袭性T细胞淋巴瘤患者的性别、肿瘤大小、是否骨髓浸润无显著相关（P〉0.05）。③年龄≤60岁患者-1306C/T的CC＋CT基因型和T等位基因分布频率显著高于年龄〉60岁患者,OR值分别为2.257（95%CI=1.031~4.942;P=0.038）和0.461（95%CI=0.260~0.812;P=0.006）。④年龄≤60岁非高危患者-418G/C的GG＋CG基因型分布显著高于高危患者（OR=2.520;95%CI=1.089~5.829;P=0.028）,年龄〉60岁非高危组患者-1306C/T的T等位基因分布较高危组患者显著增高（OR=0.171;95%CI=0.046~0.634;P=0.005）。⑤Ann Arbor分期为Ⅲ、Ⅳ期患者的-735C/T的T等位基因分布频率显著高于Ⅰ、Ⅱ期患者（OR=0.558;95%CI=0.329~0.947;P=0.029）。⑥有B症状的侵袭性T细胞淋巴瘤患者-1306C/T的T等位基因分布较无B症状患者显著增高（OR=1.796;95%CI=1.127~2.861;P=0.013）。⑦肿瘤起源于淋巴结患者-418G/C的GG＋CG基因型分布频率较起源于淋巴结外的患者显著增高（OR=0.539;95%CI=0.293~0.991;P=0.046）。⑧MMP-2-1306 C/T、-735C/T和TIMP-2-418G/C 3个SNPs的基因型分布与侵袭性T细胞淋巴瘤的3年总生存无显著相关（Log-rank检验,P〉0.05）。结论 MMP-2和TIMP-2基因启动子区多态性与侵袭性T细胞淋巴瘤疾病进展相关。【Objective】 The single nucleotide polymorphisms（SNPs） in matrix metalloproteinases-2（MMPs-2） and tissue inhibitors of metalloproteinase-2（TIMP-2） promoter region have been shown to play important roles in tumor development and adverse outcome, via modifying the transcriptional activity and further influ- encing protein expression of MMP-2 and TIMP-2. 【Methods】 Three polymorphisms were analyzed by poly- merase chain reaction-restriction fragment length polymorphism（PCR-RFLP） method in 192 patients with ag- gressive T-cell lymphoma. We examined the possible correlations between the three polymorphisms（MMP-2（-1306C/T and-735C/T） and TIMP-2 gene（-418G/C） and the clinical significance and survival rate in pa- tients with aggressive T-cell lymphoma. 【Results】 The incidence of the CC ＋ CT genotypes and T allele of 1306C/T was significantly higher in age youner than 60 years patients compared to older patients（OR=2.257; 95%CI= 1.031 ~ 4.942; P =0.038 and OR= 0.461; 95%CI= 0.260 ~ 0.812; P =0.006）. The GG ＋ CG genotypes of the-418G/C gene in age youner than 60 years patients with low/low-intermediate risk was significantly higher compared to patients with high-intermediate/high risk（OR= 2.520; 95%CI= 1.089~5.829; P =0.028）. The inci- dence of the T allele of the-1306C/T polymorphism was significantly higher in patients with low/low- inter- mediate risk was significantly higher compared to patients with high-intermediate/high risk（OR=0.171;95%CI= 0.046 ~ 0.634; P =0.005）. The T allele in patients exhibiting the-735C/T polymorphism was significantly more frequent in patients with clinical stage Ⅲ ~ Ⅳ compared to stage Ⅰ~Ⅱ（OR= 0.558; 95%CI= 0.329 ~ 0.947; P =0.029）. The incidence of the T allele of the-1306C/T polymorphism was significantly higher in patients with B-symptoms compared to those without（OR= 1.796; 95%CI= 1.127 ~ 2.861; P =0.013）. The GG ＋ CG genotypes of the-418G/C gene were significantly more frequent compared to CC genotypes in lymph node

关 键 词：侵袭 T细胞淋巴瘤 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]