artículo
A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)
Fecha
2010Registro en:
10.1016/j.ajog.2010.05.026
1097-6868
0002-9378
MEDLINE:20673868
WOS:000282287000034
Autor
Romero, Roberto
Friel, Lara A.
Edwards, Digna R. Velez
Kusanovic, Juan Pedro
Hassan, Sonia S.
Mazaki Tovi, Shali
Vaisbuch, Edi
Kim, Chong Jai
Erez, Offer
Chaiworapongsa, Tinnakorn
Pearce, Brad D.
Bartlett, Jacquelaine
Salisbury, Benjamin A.
Anant, Madan Kumar
Vovis, Gerald F.
Lee, Min Seob
Gomez, Ricardo
Behnke, Ernesto
Oyarzun, Enrique
Tromp, Gerard
Williams, Scott M.
Menon, Ramkumar
Institución
Resumen
OBJECTIVE: We sought to determine whether maternal/fetal single-nucleotide polymorphisms (SNPs) in candidate genes are associated with preterm prelabor rupture of membranes (pPROM). STUDY DESIGN: A case-control study was conducted in patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; false discovery rate was used to correct for multiple testing (q(star) = 0.15). RESULTS: First, a SNP in tissue inhibitor of metalloproteinase 2 in mothers was significantly associated with pPROM (odds ratio, 2.12; 95% confidence interval, 1.47-3.07; P = .000068), and this association remained significant after correction for multiple comparisons. Second, haplotypes for Alpha 3 type IV collagen isoform precursor in the mother were associated with pPROM ( global P = .003). Third, multilocus analysis identified a 3-locus model, which included maternal SNPs in collagen type I alpha 2, defensin alpha 5 gene, and endothelin 1. CONCLUSION: DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM.