Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease
Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease
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DOI：
10.1002/jcla.22174
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发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Cengiz, Mujgan
中科院分区：
文献类型：
--
作者：
Bayoglu, Burcu;Arslan, Caner;Cengiz, Mujgan
外周动脉疾病（peripheral artery disease，PAD）是一种影响外周循环的血管疾病.最近，全基因组关联研究揭示了ADAMTS 7（一种具有血小板反应蛋白基序7的去整合素和金属蛋白酶）的单核苷酸多态性（SNP）与动脉粥样硬化之间的关系。在这项研究中，我们的目的是确定ADAMTS 7在外周血单核细胞（PBMC）的表达和频率ADAMTS 7的rs 1994016和rs3825807多态性在样本的土耳其PAD患者，并评估相关的基质金属蛋白酶（MMP）水平与PAD的发展。分别采用逆转录实时定量聚合酶链反应（RT-qPCR）和蛋白质印迹法测定ADAMTS 7 mRNA和蛋白质表达，采用实时荧光定量PCR检测115例PAD患者和116例健康对照者ADAMTS 7基因rs 1994016和rs3825807变异。结果PAD患者ADAMTS 7 mRNA水平明显高于对照组（t=-2.75，P =.007）; rs 1994016和rs3825807在PAD患者和对照组中的频率差异无统计学意义（P> 0.05）。在PAD患者中，rs 1994016的CC基因型（t=-2.31，P =.026）和rs3825807的TT基因型（t =-2.23，P =.032）的ADAMTS 7 mRNA水平显著升高。PAD患者血浆MMP-1、MMP-3、MMP-7、MMP-10、MMP-12和MMP-13水平显著高于对照组（P
AimPeripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development.MethodsIn this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system.ResultsADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P