A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans
A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans
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DOI：
10.1093/molehr/8.5.494
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发表时间：
2002-05-01
影响因子：
4
通讯作者：
Strauss, JF
中科院分区：
文献类型：
--
作者：
Ferrand, PE;Parry, S;Strauss, JF
胎膜破裂与基质金属蛋白酶 9 (MMP-9) 表达增加和基质降解有关。我们已经确定了 MMP-9 基因中可变数量串联重复和单核苷酸多态性 (SNP) 对启动子活性的功能意义及其与早产胎膜早破 (PPROM) 的关联。在羊膜上皮细胞和 WISH 羊膜衍生细胞中，14 CA 重复等位基因是比 20 CA 重复等位基因更强的启动子，但在 THP-1 单核细胞/巨增殖细胞中，14 和 20 CA 重复等位基因具有相似的活性。 -1562 处的 SNP 不会显着影响启动子活性。一项针对非裔美国新生儿的病例对照研究显示，14 CA 重复等位基因在未足月胎膜早破母亲所生的新生儿中比足月分娩的新生儿更常见。 -1562 SNP 和 PPROM 之间没有关联。我们得出的结论是，与 CA 重复次数相关的 MMP-9 启动子活性存在细胞宿主依赖性差异，并且胎儿携带 14 CA 重复等位基因与非裔美国人的 PPROM 相关。
Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macropliage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.