A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans.
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.
Ferrand
Pedro E
PE
Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Parry
Samuel
S
Sammel
Mary
M
Macones
George A
GA
Kuivaniemi
Helena
H
Romero
Roberto
R
Strauss
Jerome F
JF
D001741:Black or African American; D000650:Amnion / Q000166:cytology / Q000502:physiology; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D020080:Tandem Repeat Sequences
D020780:Matrix Metalloproteinase 9