Molecular Human Reproduction, Vol. 8, No. 5, 494-501,
May 2002
© 2002 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans
1 Center for Research on Reproduction and Women's Health and 2 Department of Biostatistics and Clinical Epidemiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104 and 3 Perinatology Research Branch, National Institute of Child Health and Human Development, Hutzel Hospital, Detroit, MI 48201, USA
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/macrophage 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.
amnion epithelial cells/extracellular matrix/genetic association/PPROM/transcriptional control
4 To whom correspondence should be addressed at: 1354 BRB II, 421 Curie Boulevard, Philadelphia, PA 19104, USA. E-mail: jfs3{at}mail.med.upenn.edu
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