MMP-9基因-1562C>T多态性与2型糖尿病足溃疡的关联研究

Correlation between a Single Nucleotide Polymorphism-1562 C > T in MMP-9 Gene and Diabetic Foot Ulcers in Patients with T2DM

目的探讨基质金属蛋白9(matrix metalloproteinase-9,MMP-9)基因启动子单核苷酸多态性(-1562 C>T)与2型糖尿病(type 2 diabetes mellitus,T2DM)引起糖尿病足溃疡(diabetic foot ulcers,DFUs)的相关性。方法选择2010年7月—2012年12月就诊的无并发症的T2DM患者249例作为无并发症T2DM组,DFUs患者110例作为DFUs组,以及同期来医院进行健康体检的人员267例为对照组。应用聚合酶链反应(polymerase chain reaction,PCR)技术对MMP-9基因-1562C>T多态性突变区域进行扩增,并通过PCR-RFLP法检测MMP-9基因-1562C>T的CT、TT、CC基因型的分布,探讨与T2DM引起DFUs的相关性。所有的数据均采用IBM SPSS Statistics 20软件进行分析。结果3组MMP-9基因-1562 C>T基因位点发现C、T等位基因和CT、TT、CC及CT+TT基因型,不同基因型出现频率在DFUs组、无并发症T2DM组以及对照组间的分布差异有统计学意义(χ2=21.69,P<0.05)。以CC型作为对照,CT/TT型在无并发症T2DM组与对照组间比较,差异有统计学意义(OR=1.82,P=0.002,95%CI:1.26,2.65);DFUs组与健康对照组相比,差异也有统计学意义(OR=1.98,P=0.005,95%CI:1.24,3.16)。无并发症T2DM组、DFUs组和健康对照组MMP-9基因-1562 C>T的T等位基因出现频率比较,差异有统计学意义(OR=1.87,P<0.001,95%CI:1.38,2.53;OR=2.00,P=0.001,95%CI:1.35,2.98)。结论 MMP-9的异常表达对DFUs的形成以及慢性蔓延有重要作用,是足部溃疡难以愈合的主要原因之一。

Objective To investigate correlation between a single nucleotide polymorphism （ SNP） -1562 C〉T in matrix metalloproteinase-9 （MMP-9） gene and diabetic foot ulcers （DFUs） in patients with type 2 diabetes mellitus （T2DM）. Methods A total of 249 T2DM patients without complication （T2DM group）, 110 T2DM patients with DFUs （ DFUs group） and 267 controls with health examination （ control group） between July 2010 and December 2012 were re-cruited in this study. Mutation area amplification of SNP-1562 C〉T in MMP-9 gene was performed using polymerase chain reaction （ PCR） technique, and CT, TT and CC genotypic distributions of SNP -1562 C〉T in MMP-9 gene were detected using PCR-restriction fragment length polymorphism （PCR-RFLP）, and then its correlation with T2DM patients with DFUs was analyzed. All data was analyzed using IBM SPSS Statistics 20 software. Results C and T alleles and CT, TT, CC and CT＋TT genotypes were found in SNP-1562 C〉T in MMP-9 geneloci among three groups, and differ-ences of occurrence frequency of genetypes were statistically significant among three groups （χ^2 =21. 69, P〈0. 05）. CC type was used as a control, there was significant difference in CT/TT type between T2DM and control groups （ OR=1. 82, P=0. 002, 95% CI： 1. 26, 2. 65）; the difference was also statistically significant between DFUs and control groups （OR=1. 98, P=0. 005, 95% CI：1. 24, 3. 16）. There were significant differences in occurrence frequency of T allele in SNP-1562 C〉T in MMP-9 gene among three groups （ OR=1. 87, P〈0. 001, 95% CI：1. 38, 2. 53; OR=2. 00, P=0. 001, 95% CI：1. 35, 2. 98）. Conclusion Abnormal expression of MMP-9 gene may play an important role in pathogenesy and chronic pervasion of DFUs, so it is one of main causes of difficult healing of DFUs.