A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)
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Date
2010
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Abstract
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.
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.
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Keywords
chorioamnionitis, DNA variants, extracellular matrix, genetic association study, genomics, genotype, haplotype, high dimensional biology, matrix metalloproteinase, parturition, prematurity, preterm prelabor rupture of membranes, single-nucleotide polymorphism, TUMOR-NECROSIS-FACTOR, INTERLEUKIN-1 RECEPTOR ANTAGONIST, MIDTRIMESTER AMNIOTIC-FLUID, FACTOR-ALPHA GENE, SINGLE NUCLEOTIDE POLYMORPHISM, EHLERS-DANLOS-SYNDROME, FALSE DISCOVERY RATE, HUMAN UTERINE CERVIX, THAN-G POLYMORPHISM, PREMATURE-RUPTURE