A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)

Autor: Gerard Tromp, Sonia S. Hassan, Tinnakorn Chaiworapongsa, Edi Vaisbuch, Ramkumar Menon, Oyarzún E, Lara A. Friel, Roberto Romero, Ricardo Gomez, Offer Erez, Benjamin A. Salisbury, Juan Pedro Kusanovic, Chong J ai Kim, Gerald F. Vovis, Jacquelaine Bartlett, Brad D. Pearce, Min S eob Lee, Digna R. Velez Edwards, Scott M. Williams, Shali Mazaki-Tovi, Ernesto Behnke, Madan Kumar Anant
Rok vydání: 2010
Předmět:
Adult
Collagen Type IV
Male
Fetal Membranes
Premature Rupture
alpha-Defensins
medicine.medical_specialty
Candidate gene
Genotype
Mothers
Single-nucleotide polymorphism
Chorioamnionitis
Autoantigens
Polymorphism
Single Nucleotide
Receptors
Corticotropin-Releasing Hormone
Article
Collagen Type I
Andrology
Fetus
Gene Frequency
Pregnancy
Internal medicine
medicine
Humans
Protein Isoforms
Receptors
Prostaglandin E
Rupture of membranes
Genetic Association Studies
Tissue Inhibitor of Metalloproteinase-2
Endothelin-1
Models
Genetic
business.industry
Haplotype
Infant
Newborn
Case-control study
Obstetrics and Gynecology
Sequence Analysis
DNA
Odds ratio
medicine.disease
Receptors
Prostaglandin E
EP1 Subtype
Collagen
type I
alpha 2
Endocrinology
Haplotypes
Case-Control Studies
Female
Collagen
business
Procollagen
Zdroj: American Journal of Obstetrics and Gynecology. 203:361.e1-361.e30
ISSN: 0002-9378
DOI: 10.1016/j.ajog.2010.05.026
Popis: 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, 1.47–3.07; 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.
Databáze: OpenAIRE
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