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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Functionally significant SNP MMP8 promoter haplotypes and preterm premature rupture of membranes (PPROM)
Human Molecular Genetics, Volume 13, No. 21, Year 2004
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Description
Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. We identified three single nucleotide polymorphisms (SNPs) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM). The minor alleles +17 (G) and -381 (G) were in complete linkage disequilibrium. A promoter fragment containing the three minor alleles had 3-fold greater activity in chorion-like trophoblast cells (BeWo, JEG-3 and HTR-8/SVneo) compared with the major allele promoter construct. Electrophoretic mobility shift assays revealed differences in BeWo nuclear protein binding to oligonucleotides representing the -381 and -799 SNPs, suggesting that the minor alleles have reduced transcription factor binding. A case-control study of African-American neonates using allele-specific primers revealed a statistically significant association between the three minor allele haplotype, which displays the highest MMP8 promoter activity in trophoblast cells, with PPROM with an odds ratio (OR) of 4.63 (P < 0.0001), whereas the major allele promoter appeared to be protective (OR = 0.52, P < 0.0002). None of the minor alleles were individually associated with PPROM. These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes. © Oxford University Press 2004; all rights reserved.
Authors & Co-Authors
Macones, George A.
United States, Philadelphia
University of Pennsylvania
Kuivaniemi, Helena
United States, Detroit
Hutzel Women's Hospital
Tromp, Gerard C.
United States, Detroit
Hutzel Women's Hospital
Shriver, Mark D.
United States, University Park
Pennsylvania State University
Romero, Roberto J.
United States, Detroit
Hutzel Women's Hospital
Strauss, Jerome F.Iii
United States, Philadelphia
University of Pennsylvania
Statistics
Citations: 126
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1093/hmg/ddh287
ISSN:
09646906
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Study Design
Case-Control Study