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

Roberto Romero, Lara A. Friel, Digna R. Velez Edwards, Juan Pedro Kusanovic, Sonia S. Hassan, Shali Mazaki-Tovi, Edi Vaisbuch, Chong Jai Kim, Offer Erez, Tinnakorn Chaiworapongsa, Brad D. Pearce, Jacquelaine Bartlett, Benjamin A. Salisbury, Madan Kumar Anant, Gerald F. Vovis, Min Seob Lee, Ricardo Gomez, Ernesto Behnke, Enrique Oyarzun, Gerard Tromp & 2 others Scott M. Williams, Ramkumar Menon

Research output: Contribution to journalArticle

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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* = 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.

Original languageEnglish (US)
Pages (from-to)361.e1-361.e30
JournalAmerican Journal of Obstetrics and Gynecology
Volume203
Issue number4
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

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Genetic Association Studies
Rupture
Mothers
Membranes
Single Nucleotide Polymorphism
Genes
Haplotypes
Fetus
alpha-Defensins
Tissue Inhibitor of Metalloproteinase-2
Collagen Type III
Endothelin-1
Collagen Type I
Extracellular Matrix
Case-Control Studies
Protein Isoforms
Odds Ratio
Confidence Intervals
Pregnancy
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM). / Romero, Roberto; Friel, Lara A.; Velez Edwards, Digna R.; 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.

In: American Journal of Obstetrics and Gynecology, Vol. 203, No. 4, 01.10.2010, p. 361.e1-361.e30.

Research output: Contribution to journalArticle

Romero, R, Friel, LA, Velez Edwards, DR, Kusanovic, JP, Hassan, SS, Mazaki-Tovi, S, Vaisbuch, E, Kim, CJ, Erez, O, Chaiworapongsa, T, Pearce, BD, Bartlett, J, Salisbury, BA, Anant, MK, Vovis, GF, Lee, MS, Gomez, R, Behnke, E, Oyarzun, E, Tromp, G, Williams, SM & Menon, R 2010, 'A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM)', American Journal of Obstetrics and Gynecology, vol. 203, no. 4, pp. 361.e1-361.e30. https://doi.org/10.1016/j.ajog.2010.05.026
Romero, Roberto ; Friel, Lara A. ; Velez Edwards, Digna R. ; 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. / A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM). In: American Journal of Obstetrics and Gynecology. 2010 ; Vol. 203, No. 4. pp. 361.e1-361.e30.
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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* = 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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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

PY - 2010/10/1

Y1 - 2010/10/1

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, 1.47-3.07; 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.

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, 1.47-3.07; 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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