TY - JOUR
T1 - A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)
AU - Romero, Roberto
AU - Friel, Lara A.
AU - Velez Edwards, Digna R.
AU - Kusanovic, Juan Pedro
AU - Hassan, Sonia S.
AU - Mazaki-Tovi, Shali
AU - Vaisbuch, Edi
AU - Kim, Chong Jai
AU - Erez, Offer
AU - Chaiworapongsa, Tinnakorn
AU - Pearce, Brad D.
AU - Bartlett, Jacquelaine
AU - Salisbury, Benjamin A.
AU - Anant, Madan Kumar
AU - Vovis, Gerald F.
AU - Lee, Min Seob
AU - Gomez, Ricardo
AU - Behnke, Ernesto
AU - Oyarzun, Enrique
AU - Tromp, Gerard
AU - Williams, Scott M.
AU - Menon, Ramkumar
N1 - Funding Information:
This research was supported, in part, by the Perinatology Research Branch , Division of Intramural Research , Eunice Kennedy Shriver National Institute of Child Health and Human Development , National Institutes of Health , Department of Health and Human Services .
PY - 2010/10
Y1 - 2010/10
N2 - 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 (*) = 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, 1.473.07; 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.
AB - 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 (*) = 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, 1.473.07; 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.
KW - DNA variants
KW - chorioamnionitis
KW - extracellular matrix
KW - genetic association study
KW - genomics
KW - genotype
KW - haplotype
KW - high dimensional biology
KW - matrix metalloproteinase
KW - parturition
KW - prematurity
KW - preterm prelabor rupture of membranes
KW - single-nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=77957329899&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2010.05.026
DO - 10.1016/j.ajog.2010.05.026
M3 - Article
C2 - 20673868
AN - SCOPUS:77957329899
SN - 0002-9378
VL - 203
SP - 361.e1-361.e30
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
IS - 4
ER -