Lu Zhong-Qiang, Wang Yi-Min, Cao Yan-Yan, Zhang Qing-Jun, Zhang Xiang-Hong, Li Yue-Hong, Wang Heng-Shu, Xie Hui-Ling, Jiao Bao-Hua, Zhang Jian-Hui
Department of Neurosurgery, The Second Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei, 050000, PR China.
Ai Zheng. 2007 May;26(5):463-8.
BACKGROUND & OBJECTIVE: Matrix metalloproteinases (MMPs) are key enzymes involved in tumor development, invasion and metastasis. The single nucleotide polymorphisms (SNPs) in the promoter regions of MMP genes may influence tumor development and progression via modulating mRNA transcription and protein expression. This study was to explore the correlations of the promoter SNPs in MMP-3 and MMP-7 genes to susceptibility to brain astrocytoma.
The genotype of MMP-3 -1171 5A/6A and MMP-7 -181A/G polymorphisms in 236 patients with brain astrocytoma and 366 healthy controls was detected by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP).
The allelotype and overall genotype distribution of MMP-3 SNP among the astrocytoma patients and healthy controls were similar (P>0.05). Stratified by sex, age, and histological grade, the susceptibility to brain astrocytoma among the subjects with 5A/5A and 5A/6A genotypes and the subjects with 6A/6A genotype were similar(P>0.05). The overall genotype distribution of MMP-7 SNP among the astrocytoma patients and healthy controls were significantly different (P = 0.001). Compared with the A/A genotype, both the G/G and the A/G genotypes significantly increased the susceptibility to astrocytoma [sex-and age-adjusted odds ratio (OR) = 2.77 and 1.69, 95% confidence interval (CI)=1.27-6.02 and 1.01-2.84, respectively]. Stratification analysis showed that the G/G genotype significantly increased the susceptibility to astrocytoma in men (adjusted OR = 3.24, 95% CI = 1.12-9.41) and in the individuals younger than 45 years (adjusted OR = 3.16, 95% CI = 1.09-9.16). When stratified by histological grade, the A/G genotype increased the susceptibility to grade II astrocytoma by about 2 folds (adjusted OR = 2.06, 95% CI = 1.05 - 4.05), while the G/G genotype increased the susceptibility to grade II-IV astrocytoma by about 3 folds.
MMP-7 -181A/G polymorphism may influence the susceptibility to astrocytoma, while MMP-3-1171 5A/6A polymorphism has no correlation to the susceptibility.
基质金属蛋白酶（MMPs）是参与肿瘤发生、侵袭和转移的关键酶。MMP基因启动子区域的单核苷酸多态性（SNPs）可能通过调节mRNA转录和蛋白质表达影响肿瘤的发生和进展。本研究旨在探讨MMP-3和MMP-7基因启动子SNPs与脑星形细胞瘤易感性的相关性。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测236例脑星形细胞瘤患者和366例健康对照者MMP-3 -1171 5A/6A和MMP-7 -181A/G多态性的基因型。
星形细胞瘤患者和健康对照者中MMP-3 SNP的等位基因型和总体基因型分布相似（P>0.05）。按性别、年龄和组织学分级分层后，5A/5A和5A/6A基因型受试者与6A/6A基因型受试者患脑星形细胞瘤的易感性相似（P>0.05）。星形细胞瘤患者和健康对照者中MMP-7 SNP的总体基因型分布有显著差异（P = 0.001）。与A/A基因型相比，G/G和A/G基因型均显著增加星形细胞瘤易感性[性别和年龄校正比值比（OR）分别为2.77和1.69，95%置信区间（CI）分别为1.27 - 6.02和1.01 - 2.84]。分层分析显示，G/G基因型显著增加男性（校正OR = 3.24，95% CI = 1.12 - 9.41）和45岁以下个体（校正OR = 3.16，95% CI = 1.09 - 9.16）患星形细胞瘤的易感性。按组织学分级分层时，A/G基因型使II级星形细胞瘤易感性增加约2倍（校正OR = 2.06，95% CI = 1.05 - 4.05），而G/G基因型使II-IV级星形细胞瘤易感性增加约3倍。
MMP-7 -181A/G多态性可能影响星形细胞瘤易感性，而MMP-3-1171 5A/6A多态性与易感性无关。
