Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

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

doi:10.1016/j.ajog.2010.03.026

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

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

Ramkumar Menon

^*Corresponding author for this work

National Institutes of Health
Wayne State University
Vanderbilt University
Emory University
Forest Laboratories, Inc
Helix Therapeutics LLC
Hospital Dr. Sotero del Rio
Pontificia Universidad Católica de Chile

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

Abstract

Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.

Original language	English
Pages (from-to)	431.e1-431.e34
Journal	American Journal of Obstetrics and Gynecology
Volume	202
Issue number	5
DOIs	https://doi.org/10.1016/j.ajog.2010.03.026
State	Published - May 2010
Externally published	Yes

Funding

Funders	Funder number
National Institutes of Health
National Institute of General Medical Sciences	T32GM080178
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Department of Health and Human Services, State Government of Victoria

Keywords

DNA variants
IL-6
SNP
chorioamnionitis
extracellular matrix
genetic association study
genotype
haplotype
parturition

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10.1016/j.ajog.2010.03.026

Cite this

Romero, R., Velez Edwards, D. R., Kusanovic, J. P., Hassan, S. S., Mazaki-Tovi, S., Vaisbuch, E., Kim, C. J., Chaiworapongsa, T., Pearce, B. D., Friel, L. A., Bartlett, J., Anant, M. K., Salisbury, B. A., Vovis, G. F., Lee, M. S., Gomez, R., Behnke, E., Oyarzun, E., Tromp, G., ... Menon, R. (2010). Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes. American Journal of Obstetrics and Gynecology, 202(5), 431.e1-431.e34. https://doi.org/10.1016/j.ajog.2010.03.026

@article{a42d17eb217e4afa94901ee0f973cca3,

title = "Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes",

abstract = "Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.",

keywords = "DNA variants, IL-6, SNP, chorioamnionitis, extracellular matrix, genetic association study, genotype, haplotype, parturition",

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

note = "Funding Information: Supported in part by the Perinatology Research Branch , Division of Intramural Research , Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH , DHHS . Drs Anant, Salisbury, and Vovis were formerly of Genaissance Pharmaceuticals, Inc., New Haven, CT, where contributions to this work were initiated. Research Obstetrics ",

year = "2010",

month = may,

doi = "10.1016/j.ajog.2010.03.026",

language = "אנגלית",

volume = "202",

pages = "431.e1--431.e34",

journal = "American Journal of Obstetrics and Gynecology",

issn = "0002-9378",

publisher = "Elsevier Inc.",

number = "5",

}

Romero, R, Velez Edwards, DR, Kusanovic, JP, Hassan, SS, Mazaki-Tovi, S, Vaisbuch, E, Kim, CJ, Chaiworapongsa, T, Pearce, BD, Friel, LA, Bartlett, J, Anant, MK, Salisbury, BA, Vovis, GF, Lee, MS, Gomez, R, Behnke, E, Oyarzun, E, Tromp, G, Williams, SM & Menon, R 2010, 'Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes', American Journal of Obstetrics and Gynecology, vol. 202, no. 5, pp. 431.e1-431.e34. https://doi.org/10.1016/j.ajog.2010.03.026

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes. / Romero, Roberto; Velez Edwards, Digna R.; Kusanovic, Juan Pedro et al.
In: American Journal of Obstetrics and Gynecology, Vol. 202, No. 5, 05.2010, p. 431.e1-431.e34.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

AU - Romero, Roberto

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 - Chaiworapongsa, Tinnakorn

AU - Pearce, Brad D.

AU - Friel, Lara A.

AU - Bartlett, Jacquelaine

AU - Anant, Madan Kumar

AU - Salisbury, Benjamin A.

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: Supported in part by the Perinatology Research Branch , Division of Intramural Research , Eunice Kennedy Shriver National Institute of Child Health and Human Development , NIH , DHHS . Drs Anant, Salisbury, and Vovis were formerly of Genaissance Pharmaceuticals, Inc., New Haven, CT, where contributions to this work were initiated. Research Obstetrics

PY - 2010/5

Y1 - 2010/5

N2 - Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.

AB - Objective: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. Study Design: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. Results: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P = .000148) and tissue inhibitor of metalloproteinase 2 (mother; P = .000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P = .004 and .007, respectively). Conclusion: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.

KW - DNA variants

KW - IL-6

KW - SNP

KW - chorioamnionitis

KW - extracellular matrix

KW - genetic association study

KW - genotype

KW - haplotype

KW - parturition

UR - https://www.scopus.com/pages/publications/77951824756

U2 - 10.1016/j.ajog.2010.03.026

DO - 10.1016/j.ajog.2010.03.026

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 20452482

AN - SCOPUS:77951824756

SN - 0002-9378

VL - 202

SP - 431.e1-431.e34

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

IS - 5

ER -

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

Abstract

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Keywords

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