MMP-9和TIMP-1基因多态性与糖尿病足的相关性研究
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摘要
目的研究基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制物-1(TIMP-1)基因多态性与糖尿病足的相关性。方法采集健康者(72例)、2型糖尿病无糖尿病足患者(69例)和2型糖尿病糖尿病足患者(65例)外周抗凝血3mL,提取外周血基因组DNA,采用高分辨率熔解曲线技术检测MMP-9基因-1562C>T和TIMP-1基因-9830T>G位点基因型和等位基因频率。结果糖尿病足患者MMP-9基因-1562位点T等位基因频率明显高于健康者和无糖尿病足患者(P<0.05),TIMP-1基因-9830T>G基因型和基因频率与健康者、无糖尿病足患者比较差异无统计学意义(P>0.05)。结论 MMP-9基因-1562T等位基因型可能是糖尿病足的易感因素。
Objective To investigate the association of matrix metalloproteinase-9(MMP-9)and tissue inhibitors of matrix metalloproteinases-1(TIMP-1)gene polymorphism with diabetic foot.Methods Peripheral blood genomic DNA was extracted from healthy subjects(72 cases),patients with type 2 diabetes but without diabetic foot(69 cases)and patients with type 2 diabetes and diabetic foot(65 cases).Genotype and allelic frequencies of MMP-9 gene-1562 C>T and TIMP-1 gene-9830 T>G loci were detected by using high resolution melting curve technique.Results The T allele frequency of MMP-9 gene-1562 in patients with diabetic foot was significantly higher than healthy subjects and patients without without diabetic foot(P<0.05).There was no significant difference in TIMP-1 gene-9830 T>G genotype and gene frequency among the three groups(P>0.05).Conclusion MMP-9 gene-1562 Tallele might be a susceptible factor for diabetic foot.
Objective To investigate the association of matrix metalloproteinase-9(MMP-9)and tissue inhibitors of matrix metalloproteinases-1(TIMP-1)gene polymorphism with diabetic foot.Methods Peripheral blood genomic DNA was extracted from healthy subjects(72 cases),patients with type 2 diabetes but without diabetic foot(69 cases)and patients with type 2 diabetes and diabetic foot(65 cases).Genotype and allelic frequencies of MMP-9 gene-1562 C>T and TIMP-1 gene-9830 T>G loci were detected by using high resolution melting curve technique.Results The T allele frequency of MMP-9 gene-1562 in patients with diabetic foot was significantly higher than healthy subjects and patients without without diabetic foot(P<0.05).There was no significant difference in TIMP-1 gene-9830 T>G genotype and gene frequency among the three groups(P>0.05).Conclusion MMP-9 gene-1562 Tallele might be a susceptible factor for diabetic foot.
引文
[1]许樟荣.糖尿病足病的诊治与预防[J/CD].中华损伤与修复杂志:电子版,2014,9(2):118-122.
[2]PADALA C,TUPURANI MA,PURANAM K,et al.Synergistic effect of collagenase-1(MMP1),stromelysin-1(MMP3)and gelatinase-B(MMP9)gene polymorphisms in breast cancer[J].PLoSOne,2017,12(9):1-19.
[3]WANG HX,YANG QD,LIU BQ,et al.TIMP-1polymorphisms in a Chinese Han population with intracerebral hemorrhage[J].Int J Neurosci,2014,124(1):61-67.
[4]YASMIN,MCENIERY CM,O′SHAUGHNESSY KM,et al.Variation in the human matrix metalloproteinase-9gene is associated with arterial stiffness in healthy individuals[J].Arterioscler Thromb Vasc Biol,2006,26(8):1799-1805.
[5]许樟荣.于世界糖尿病日重谈糖尿病足的诊治与预防[J].中华内分泌代谢杂志,2005,21(6):491-493.
[6]WANG A,XU Z,MU Y,et al.Clinical characteristics and medical costs in patients with diabetic amputation and nondiabetic patients with nonacute amputation in central urban hospitals in China[J].Int J Low Extrem Wounds,2014,13(1):17-21.
[7]王玉珍,许樟荣.住院糖尿病足病临床诊治指南[J].药品评价,2013,6(17):43-45.
[8]OPSTAD TB,ARNESEN H,PETTERSEN AA,et al.The MMP-9-1562C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease[J].PLoS One,2014,9(9):1-7.
[9]ZHANG ZW,WU XY,CAI T,et al.Matrix metalloproteinase 9gene promoter(rs 3918242)mutation reduces the risk of diabetic microvascular complications[J].Int J Environ Res Public Health,2015,12(7):8023-8033.
[10]PRASETYO E,ASADUL ISLAM A,HATTA M,et al.The profile of MMP-9,MMP-9 mRNA expression,-1562C/T polymorphism and outcome in high-risk traumatic brain injury:the effect of therapeutic mild hypothermia[J].Neurol Med Chir(Tokyo),2017,57(11):612-619.
[11]陈占玲,李春华,孙庆凯,等.糖尿病足患者血清基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1水平检测[J].广东医学院学报,2016,34(2):121-123.
[12]SINGH K,AGRAWAL NK,GUPTA SK,et al.A functional single nucleotide polymorphism-1562C>T in the matrix metalloproteinase-9promoter is associated with type 2diabetes and diabetic foot ulcers[J].Int J Low Extrem Wounds,2013,12(3):199-204.
[13]刘宽芝,陈雅静,王战建,等.基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究[J].中华内分泌代谢杂志,2003,19(6):24-26.
[2]PADALA C,TUPURANI MA,PURANAM K,et al.Synergistic effect of collagenase-1(MMP1),stromelysin-1(MMP3)and gelatinase-B(MMP9)gene polymorphisms in breast cancer[J].PLoSOne,2017,12(9):1-19.
[3]WANG HX,YANG QD,LIU BQ,et al.TIMP-1polymorphisms in a Chinese Han population with intracerebral hemorrhage[J].Int J Neurosci,2014,124(1):61-67.
[4]YASMIN,MCENIERY CM,O′SHAUGHNESSY KM,et al.Variation in the human matrix metalloproteinase-9gene is associated with arterial stiffness in healthy individuals[J].Arterioscler Thromb Vasc Biol,2006,26(8):1799-1805.
[5]许樟荣.于世界糖尿病日重谈糖尿病足的诊治与预防[J].中华内分泌代谢杂志,2005,21(6):491-493.
[6]WANG A,XU Z,MU Y,et al.Clinical characteristics and medical costs in patients with diabetic amputation and nondiabetic patients with nonacute amputation in central urban hospitals in China[J].Int J Low Extrem Wounds,2014,13(1):17-21.
[7]王玉珍,许樟荣.住院糖尿病足病临床诊治指南[J].药品评价,2013,6(17):43-45.
[8]OPSTAD TB,ARNESEN H,PETTERSEN AA,et al.The MMP-9-1562C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease[J].PLoS One,2014,9(9):1-7.
[9]ZHANG ZW,WU XY,CAI T,et al.Matrix metalloproteinase 9gene promoter(rs 3918242)mutation reduces the risk of diabetic microvascular complications[J].Int J Environ Res Public Health,2015,12(7):8023-8033.
[10]PRASETYO E,ASADUL ISLAM A,HATTA M,et al.The profile of MMP-9,MMP-9 mRNA expression,-1562C/T polymorphism and outcome in high-risk traumatic brain injury:the effect of therapeutic mild hypothermia[J].Neurol Med Chir(Tokyo),2017,57(11):612-619.
[11]陈占玲,李春华,孙庆凯,等.糖尿病足患者血清基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1水平检测[J].广东医学院学报,2016,34(2):121-123.
[12]SINGH K,AGRAWAL NK,GUPTA SK,et al.A functional single nucleotide polymorphism-1562C>T in the matrix metalloproteinase-9promoter is associated with type 2diabetes and diabetic foot ulcers[J].Int J Low Extrem Wounds,2013,12(3):199-204.
[13]刘宽芝,陈雅静,王战建,等.基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究[J].中华内分泌代谢杂志,2003,19(6):24-26.