Demacq Caroline, de Souza Ana P, Machado Alcyone A, Gerlach Raquel F, Tanus-Santos Jose E
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Clin Chim Acta. 2006 Mar;365(1-2):183-7. doi: 10.1016/j.cca.2005.08.017. Epub 2005 Sep 15.
Plasma MMP-9 levels have been shown to predict cardiovascular risk, and a functional substitution C to T at position -1562 in the promoter region of the MMP-9 gene has been associated with the severity of cardiovascular diseases. We examined the association between the C(-1562)T polymorphism and MMP-9 activity in healthy subjects.
We studied 200 healthy male white volunteers (age range: 20-55 y) who were nonsmokers and were not taking medicines. Genomic DNA was extracted and genotypes for the C(-1562)T polymorphism were determined by PCR and restriction fragment length digestion. Plasma was assayed for pro-MMP-9 and MMP-9 activities by gelatin zymography.
The frequency of the alleles "C" and "T" were 90% and 10%, respectively. Because of the relatively low frequency of the TT genotype, we combined both TT and CT genotypes together (CT+TT group) and compared with the CC genotype group. We found no differences in pro-MM9 and MMP-9 activity levels among the genotype groups (both P>0.05).
While the present study indicates lack of effect for the C(-1562)T polymorphism on MMP-9 activity in plasma, it is possible that the C(-1562)T polymorphism contributes to an increased cardiovascular risk under conditions of induced MMP-9 expression.
血浆基质金属蛋白酶-9(MMP-9)水平已被证明可预测心血管风险,且MMP-9基因启动子区域-1562位的功能性C到T替换与心血管疾病的严重程度相关。我们研究了健康受试者中C(-1562)T多态性与MMP-9活性之间的关联。
我们研究了200名健康男性白人志愿者(年龄范围:20 - 55岁),他们不吸烟且未服用药物。提取基因组DNA,通过聚合酶链反应(PCR)和限制性片段长度消化确定C(-1562)T多态性的基因型。通过明胶酶谱法检测血浆中的前MMP-9和MMP-9活性。
等位基因“C”和“T”的频率分别为90%和10%。由于TT基因型频率相对较低,我们将TT和CT基因型合并在一起(CT + TT组)并与CC基因型组进行比较。我们发现各基因型组之间的前MMP-9和MMP-9活性水平无差异(均P>0.05)。
虽然本研究表明C(-1562)T多态性对血浆中MMP-9活性没有影响,但在诱导MMP-9表达的条件下,C(-1562)T多态性可能会增加心血管风险。