Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate

Tracy A. Manuck; Yinglei Lai; Paul J. Meis; Mitchell P. Dombrowski; Baha Sibai; Catherine Y. Spong; Dwight J. Rouse; Celeste P. Durnwald; Steve N. Caritis; Ronald J. Wapner; Brian M. Mercer; Susan M. Ramin

doi:10.1016/j.ajog.2011.03.048

Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate

Tracy A. Manuck, Yinglei Lai, Paul J. Meis, Mitchell P. Dombrowski, Baha Sibai, Catherine Y. Spong, Dwight J. Rouse, Celeste P. Durnwald, Steve N. Caritis, Ronald J. Wapner, Brian M. Mercer, Susan M. Ramin

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

58 Scopus citations

Abstract

Objective: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB. Study Design: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering <37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553. Conclusion: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.

Original language	English (US)
Pages (from-to)	135.e1-135.e9
Journal	American journal of obstetrics and gynecology
Volume	205
Issue number	2
DOIs	https://doi.org/10.1016/j.ajog.2011.03.048
State	Published - Aug 2011
Externally published	Yes

Keywords

17-alpha hydroxyprogesterone caproate
genetic polymorphisms
progesterone receptor
recurrent preterm birth

ASJC Scopus subject areas

Obstetrics and Gynecology

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10.1016/j.ajog.2011.03.048

Cite this

Manuck, T. A., Lai, Y., Meis, P. J., Dombrowski, M. P., Sibai, B., Spong, C. Y., Rouse, D. J., Durnwald, C. P., Caritis, S. N., Wapner, R. J., Mercer, B. M., & Ramin, S. M. (2011). Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate. American journal of obstetrics and gynecology, 205(2), 135.e1-135.e9. https://doi.org/10.1016/j.ajog.2011.03.048

Manuck, TA, Lai, Y, Meis, PJ, Dombrowski, MP, Sibai, B, Spong, CY, Rouse, DJ, Durnwald, CP, Caritis, SN, Wapner, RJ, Mercer, BM & Ramin, SM 2011, 'Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate', American journal of obstetrics and gynecology, vol. 205, no. 2, pp. 135.e1-135.e9. https://doi.org/10.1016/j.ajog.2011.03.048

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title = "Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate",

abstract = "Objective: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB. Study Design: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering <37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553. Conclusion: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.",

keywords = "17-alpha hydroxyprogesterone caproate, genetic polymorphisms, progesterone receptor, recurrent preterm birth",

author = "Manuck, {Tracy A.} and Yinglei Lai and Meis, {Paul J.} and Dombrowski, {Mitchell P.} and Baha Sibai and Spong, {Catherine Y.} and Rouse, {Dwight J.} and Durnwald, {Celeste P.} and Caritis, {Steve N.} and Wapner, {Ronald J.} and Mercer, {Brian M.} and Ramin, {Susan M.}",

note = "Funding Information: The project described was supported by the following grant numbers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): HD27860 , HD36801 , HD27917 , HD21414 , HD27861 , HD27869 , HD27905 , HD34208 , HD34116 , HD21410 , HD27915 , HD34136 , HD34210 , HD34122 , HD40500 , HD40544 , HD34116 , HD40560 , and HD40512 . This paper does not necessarily represent the official views of the NICHD or National Institutes of Health. ",

year = "2011",

month = aug,

doi = "10.1016/j.ajog.2011.03.048",

language = "English (US)",

volume = "205",

pages = "135.e1--135.e9",

journal = "American journal of obstetrics and gynecology",

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T1 - Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate

AU - Manuck, Tracy A.

AU - Lai, Yinglei

AU - Meis, Paul J.

AU - Dombrowski, Mitchell P.

AU - Sibai, Baha

AU - Spong, Catherine Y.

AU - Rouse, Dwight J.

AU - Durnwald, Celeste P.

AU - Caritis, Steve N.

AU - Wapner, Ronald J.

AU - Mercer, Brian M.

AU - Ramin, Susan M.

N1 - Funding Information: The project described was supported by the following grant numbers from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): HD27860 , HD36801 , HD27917 , HD21414 , HD27861 , HD27869 , HD27905 , HD34208 , HD34116 , HD21410 , HD27915 , HD34136 , HD34210 , HD34122 , HD40500 , HD40544 , HD34116 , HD40560 , and HD40512 . This paper does not necessarily represent the official views of the NICHD or National Institutes of Health.

PY - 2011/8

Y1 - 2011/8

N2 - Objective: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB. Study Design: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering <37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553. Conclusion: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.

AB - Objective: Seventeen-alpha-hydroxyprogesterone caproate (17-OHPC) reduces recurrent preterm birth (PTB). We hypothesized that single nucleotide polymorphisms in the human progesterone receptor (PGR) affect response to 17-OHPC in the prevention of recurrent PTB. Study Design: We conducted secondary analysis of a study of 17-OHPC vs placebo for recurrent PTB prevention. Twenty PGR gene single nucleotide polymorphisms were studied. Multivariable logistic regression assessed for an interaction between PGR genotype and treatment status in modulating the risk of recurrent PTB. Results: A total of 380 women were included; 253 (66.6%) received 17-OHPC and 127 (33.4%) received placebo. In all, 61.1% of women were African American. Multivariable logistic regression demonstrated significant treatment-genotype interactions (either a beneficial or harmful treatment response) for African Americans delivering <37 weeks' gestation for rs471767 and rs578029, and for Hispanics/Caucasians delivering <37 weeks' gestation for rs500760 and <32 weeks' gestation for rs578029, rs503362, and rs666553. Conclusion: The clinical efficacy and safety of 17-OHPC for recurrent PTB prevention may be altered by PGR gene polymorphisms.

KW - 17-alpha hydroxyprogesterone caproate

KW - genetic polymorphisms

KW - progesterone receptor

KW - recurrent preterm birth

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ER -

Progesterone receptor polymorphisms and clinical response to 17-alpha-hydroxyprogesterone caproate

Abstract

Keywords

ASJC Scopus subject areas

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